SPACE BIOLOGY AND AEROSPACE MEDICINE,

NO. 3, 1977

Jiont Publications Research Service

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Jul 77

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1. Report No.

JPRS 69 380

4. Title and Subtitle

SPACE BIOLOGY AND AEROSPACE MEDICINE, No. 3, 19 77

3. Recipient's Accession No.

5. Report Date

7 July 19 77

7. Author(s)

9. Performing Organization Name and Address

Joint Publications Research Service

1000 North Glebe Road

Arlington, Virginia 22201

12. Sponsoring Organization Name and Address

As above

8. Performing Organization Rept.

No.

10. Project/Task/Work Unit No.

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13. Type of Report & Period

Covered

14.

15. Supplementary Notes

Cover-to-cover translation of KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICKESKAYA

MEDITSINA, bimonthly journal, published by the USSR Ministry of Health.

16. Abstracts

The report contains articles concerning the selection and training of cosmonauts;

evaluation and analysis of accumulated data to facilitate the on-going transition

from orbital to interplanetary flights; research aimed at guaranteeing safety on

long flights and reliability of the human component of the "man-spaceship" system;

space psychology and physiology; environmental problems and control (spacecraft

habitability, effects of radiation and weightlessness, etc.) and telemetry.

17. Key Words and Document Analysis. 17a. Descriptors

USSR

Exobiology

Life Support

Human Factors Engineering

Confined Environments

Stress (Psychology)

Aerospace Environment

Biotelemetry

17b. Identifiers /Open-Ended Terms

17e. COSATI lield/C-roup 6S, 6K

18. Avniluliiltry Statement

Unlimited Availability

Sold by NTIS

Springfield, Virginia 22151

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Report)

20. Security Class (This

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UNCLASSIFIED

21. No. of Pages

136

22. Price

roHM N riS'Su i««v. s-7ji THIS FORM MAY RK REPRODUCED

USCOMM-DC M9i2-P72
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( i )
CONTENTS (Continued) PaS

e

Cardiovascular Reactions to Orthostatic Tests and Human Resistance

to Vestibular Stimuli

(B. I. Polyakov, et al.) 62

Dynamic Control of Parameters of Spacecraft Atmosphere

(I. S. Breslav, V. N. Salazkin) 68

Mechanics of Speech-Related Respiration While Performing Static

Physical Exercise

(M. A. Tikhonov, A. S. Belan) 76

Electrolyte Content of Blood and Potassium Ion Transport in

Erythrocytes of Animals Exposed to a Steady Magnetic Field

(G. K. Gerasimova, Z. N. Nakhil'nitskaya) 83

Hemopoiesis in Dogs Exposed to Lethal Doses of Protons With Shielded

Bone Marrow

(G. F. Nevskaya, et al.) 88

Investigation of Concomitant Microflora in Prolonged Substrate-Free

Cultivation of Beet Plants

(L. S. Yunusova, N. A. Drugova) 93

Physiology of Antiorthostatism

(K. L. Geykhman, M. R. Mogendovich) 97

Heterophilic Antibodies and Complement Activity of Rat Blood Serum

After Flight in Kosmos-605 Satellite

(V. V. Portugalov, et al.) 102

Measurement of Radiation Doses in the Soyuz-16 Spacecraft

(Yu. A. Akatov, et al.) 1°6

Blood Clotting Function During 12-Day Immersion in Water, and the

Preventive Role of Revolving on a Centrifuge

(M. A. Khudyakova, Ye. B. Shul'zhenko) 108

Defense Reactions of the Organism While Breathing High

Concentrations of Carbon Dioxide

(0. Yu. Sidorov, Z. K. Sulimo-Samuyllo) 113

Effect of Gamma Radiation on Intensity of Ammonia Excretion in

Albino Rats

(K. P. Bugar', et al.). 117

ne - b -
JPRS 69380

7 July 19 77

SPACE BIOLOGY AND AEROSPACE MEDICINE

No. 3, 19 77

Complete translation of the Russian-language periodical

KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA

published in Moscow by the Meditsina Izdatel'stvo

CONTENTS PAGE

Psychopharmacology in Aviation and Astronautics

(P. V. Vasil'yev, G. D. Glod) 1

Condition of Microscopic and Crystalline Structures, Microconsistency

and Mineralization of Human Bone Tissue Following a Long Space Flight

(0. G. Gazenko, et al.),... 15

Distinctive Features of Regional Circulation and Vasomotor Regulation

Following a Two-Month Space Flight

(Kh. Kh. Yarullin, T. D. Vasil'yeva) .. . 25

Studies of Circulation During LBNP Test Aboard Salyut-4 Orbital Station

(V. A. Degtyarev, et al.) 33

Dynamics of Orthostatic Stability of Cosmonauts Following 2 to 63-Day

Missions

(V. V. Kalinichenko) 39

Some Psychoneurological Requirements in Assessing Inflight Functional

State of Cosmonauts

(V. I. Myasnikov, et al.) 46

Histochemical Study of Digestive Organs of Rats Following Flight on

Kosmos-605

(M. G. Shubich, et al.) 50

Mucopolysaccharides and Collagen of Tissues in Hypokinetic Rats

(P. P. Potapov). 56

ilii - a- [III - USSR - 20-H S$T]
CONTENTS (Continued) Page

Otolith System Function in Cosmonauts Following Space Missions

(F. A. Solodovnik) 121

Sudden Loss of Consciousness in Pilots With Low Intraocular Pressure

During Exposure to G Forces

(Yu. Domashuk, M. Voytkovyak) lz4

New Book Deals With Physiological Functions of the Vestibular System

(A. Ye. Kurashvili, V. I. Babiyak) 126

Biography of Yuvenaliy Mikhaylovich Volynkin (On His 70th Birthday).. 129

Obituary of Sergey Pavlovich Korelev (On His 70th Birthday) 131
PUBLICATION DATA

English title of journal : Space Biology and Aerospace Medicine,

No 3, 1977

Russian title of journal : Kosmicheskaya Biologiya i Aviakosmicheskaya

Meditsina

Editor (s) 0. G. Gazenko

Publishing House Izdatel'stvo Meditsina

Signed to press 13 April 1977

Copies 1,708

COPYRIGHT Kosmicheskaya Biologjya i Aviakosmicheskaya

Meditsina, 1977

III - d
SURVEYS

UDC: 615.214.03:613.693

PSYCHOPHARMACOLOGY IN AVIATION AND ASTRONAUTICS

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 3-11

[Article by P. V. Vasil'yev and G. D. Glod, submitted 20 Jul 76]

[Text] The refinement of aerospace technology has a substantial effect on

the nature of professional activity of crews, making it increasingly tense

and responsible. As a result there may be stress and depletion of compensatory reactions and, as a consequence, diminished efficiency of crew

members involved in regular and particularly unforeseen flying conditions.

The foregoing convinces us of the urgency of searching for new ways and means

of maintaining a high degree of efficiency and professional reliability of

crews.

In this regard, pharmacological agents with psychotropic action are of some

promise. The theoretical and applied aspects of using psychopharmacological

agents (PPA) in aerospace medicine are quite diverse (see Chart).

Each of them merits special consideration. However, the pathogenesis of

impaired efficiency of pilots and astronauts in flight and the capabilities

of current PPA give us grounds to consider two main directions of application of PPA to be the most promising at the present time: for the prevention

or correction of functional disturbances in the central nervous system that

are related to fatigue, and for controlled regulation of emotions.

The use of PPA as levers to control the functional state of the organism increases efficiency and professional reliability of the [human] operator

under standard and particularly extreme operating conditions. The following

special problems are being resolved on the way toward this ultimate goal:

reduction of signs of fatigue and maintenance of a high degree of efficiency;

emergency mobilization of psychophysiological functions when necessary;

prolonged and stable increase of efficency; regulation of processes of adaptation to new and unusual conditions; curbing excessive emotional reactions;

prevention of stress and nervous breakdown; increasing resistance of the

organism to some deleterious factors, etc.
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There is a history to the control of fatigue by means of PPA with psychostimulating action. Man's first attempts to artificially increase his

efficiency go back to antiquity. In ancient Rome, the stimulant beverage,

hydromel, was used [93]. Philostratus and Galen reported that athletes

took stimulants at Olympic games to improve their athletic achievements [63].

In Russia, such medicinal plants as the tea plant [Lycium barbarum L.],

"levzeya" [probably snapdragon family] and lemon tree [could be Schizandra

also] were used since olden times [45]. In the years of the Great Patriotic

War, phenylalkylamines and cola products were used in the armies of belligerent countries, including our air corps [10, 23, 27, 47, 48, 50-53, and

others]. The cited authors reported that the psychostimulants were rather

effective, but indicated that efforts to mobilize psychophysiological functions immediately and appreciably were limited in many respects by the

side-effects of phenamine and rather frequent instances (up to 15%) of paradoxical reactions to the drug.

In postwar years, there was significant decrease in interest of researchers

in the problem of psychostimulants. Nor was it developed and applied in

the field of athletics, because of the negative attitude toward drug addiction ["doping"]. It is only in the last few decades, against the background

of increased interest in problems of psychopharmacological regulation of

functional state of the organism that a series of works was published,

dealing with research and comprehensive clinicopharmacological investigation

of new representatives in this group of products. Thanks to the research

of I. I. Brekhman, A. S. Saratikov, A. D. Turova and a number of other

authors, a new group of stimulants of plant origin was adopted in clinical

practice (eleuterococcus, ginseng family [Araliaceae], "gold root," etc.),

administration of which for "pharmacohygienic" purposes [18], i.e., to

maintain stable physical and mental efficiency for a long time in a

healthy and active individual, elicits some effect. New products were

also developed (phenatine, sydnocarb, sydnophen, piridrol, meridil, etc.)

that could be considered as fast-acting stimulants [3-8, 40, 41, 43, 55,

and others]. The products were submitted to comprehensive investigation

as to their clinical applications, and several works have demonstrated

their superiority to phenamine. At the present time, there are publications

reporting the beneficial effects of PPA with simulant action and general

tonics in the presence of fatigue as related to some types of activities

[8. 13, 15, 20-22, 37, 65, 89, 103, 104, and others]. In the foreign

literature, attention is concentrated primarily on various derivatives of

amphetamines.

The pharmacodynamic properties of phenamine and its numerous analogues and

derivatives are considered quite important from the standpoint of pathogenesis of disorders and probable functional disturbances associated with

fatigue. The products stimulate such human qualities as optimism and selfconfidence [100]; they increase efficiency in the case of sleep deprivation

[89, 104] or markedly lowered motivation [65, 74, 80, 101]; they increase

tolerance of conflict situations [85]; they improve significantly the

quality of performance of tests that require stable motor coordination [72],

etc. However, the unanimous opinion of specialists is that PPA of the

phenamine type can be considered solely as emergency aids under particularly
difficult working conditions [22, 48, 58, 78, and others]. Regular intake

of products in this group is absolutely inadmissible, since it depletes

catecholamines in tissular reservoirs, with decrease in adaptive capabilities of the organism under sharply changing environmental conditions 19,

30, 62, 77, 87, and others].

Thus, data have now been accumulated, on the basis of which it is possible

to make a primary selection of PPA with psychostimulant action to be

followed by comprehensive experimental research on suitability thereof tor

aerospace medical practice.

Questions of optimizing the conditions under which man works and to maintain

a high level of efficiency by means of regulating emotions with anxiolytic

PPA were raised very recently in view of the discovery of this group of

agents. The data published in recent years [2, 16, 22, 25, Jl, Jö, J» , <*?,

75 92 97 and others) are indicative of the need for a very careful study

of'agents in this group from the standpoint of interests of aerospace medicine Data are cited in the literature on the capacity of anxiolytics not

only to alleviate subjective and autonomic components of emotional stress

during intensive activity, but to retain efficiency to a significant extent.

Ruesg et al. [97], who tested the effect of elenium on fitness [efficiency]

of candidates for pilots in the Swiss army, established that this product

has an adverse effect on fitness only when taken in large doses (0.04 g).

In doses of 0.01-0.02 g, elenium did not alter the capacity for concentration, complex psychomotor acts and other parameters.

The research of Patejdl et al. [91] revealed that meprobamate had a beneficial

effect on shooting performance. 0. S. Lobastov et al. [39] recommends elenium

for riflemen that have a predisposition for nervous breakdowns. N. b.

Kuz'mich et al. [36] obtained good results in their tests of trioxazine

in paratroopers making jumps from low altitudes. V. P. Berezhnoy [16]

reports that trioxazine is effective in lowering emotional tension of young

soldiers during firing of guns. It was established that this agent attenuates autonomic reactions and improves the technical results of shooting.

Holliday [79], Davies [69] and others have reported the beneficial effect

of anxiolytics on physiological reactions and efficiency in stress situations.

Apparently, the beneficial effects of these agents on efficiency are related

primarily to their capacity to preserve purposeful tension at an optimum

level, exceeding which results in disorganization of performance of the

operator [42, 57, 76, 84, and others].

Analysis of the literature describing the pharmacological properties of the

most popular representatives of anxiolytics reveals that not all of them

are of equal interest to experimental investigation related to objectives

of aerospace medicine. All of the products in this group (with the exception

of trioxazine) are characterized in the literature as not being safe for

individuals whose occupation requires rapid mental and motor reactions U, 2,

40, 54, and others]. For example, according to the data of L. Kosha U-u,

5
the advantage of trioxazine over other anxiolytics is that while it does

lower overexcitability, inhibit impulsive emotional reactivity, eliminate

fear and depression, its toxicity is very low and, in therapeutic doses, it

does not induce drowsiness, listlessness, depression cf intellectual

activity and it does not have a myorelaxant effect or other undesirable

effects. The myorelaxant action that is inherent in most anxiolytics,

which induce either drowsiness (elenium, seduxen, meprobramate) or impairment of vision (amizil) is unquestionably one of their undesirable sideeffects. In this regard, the warnings of many authors [56, 68, 82, 102,

and others] about the danger of having flight personnel take various pharmacological agents with marked side-effects must be considered completely

justified.

However, it should be borne in mind that this group of agents was investigated primarily in the aspect of clinical medicine. The described undesirable side-effects are usually demonstrable in the spectrum of pharmacological activity when large doses are prescribed or when they are

taken regularly for a long period of time. There has not been sufficient

investigation of the effects of single preventive intake of anxiolytics by

healthy individuals. There is virtually no information in the literature

about studies dealing with enhancement of beneficial aspects and attenuation of undesirable ones in the spectrum of pharmacological activity of

anxiolytics. The question of choice of agent to curb the negative effects

due to emotional tension of diverse genesis has not yet been definitively

answered. In the opinion of A. V. Val'dman [19], Dews [71] and others,

pharmacological regulation should be implemented with agents varying in type

of action, depending on the nature of the provocative factor and neurophysiological mechanisms that are functional at a given stage of development

of the stress reaction.

The solution to these and a number of other pressing problems of psychopharmacology will aid in successful implementation of clinical use of PPA with

anxiolytic action.

The answer to the question of choice of PPA that would be suitable for

their purpose, implies the purposeful synthesis of new substances with predetermined spectrum of pharmacological activity, on the basis of medicotechnical specifications that are being worked out and choice of agents

among those that have been well-studied and submitted to extensive clinical

trial.

According to the data of Berde [61], it takes 7-11 years to develop a new

drug, which requires considerable expense and labor. According to this

author, just to advance this process to the stage of clinical investigation requires a mean of 150 man-years in labor units. The second direction

also cannot be limited to simple choice of agents on the basis of data in

the literature, and it will require special experimental research with due

consideration of the specific conditions under which the products plan to

be used. In our opinion, PPA intended to correct an altered functional

state in pilots and astronauts during flights should, first of all, be
free of any deleterious effects on professional efficiency and endurance

of typical Stressors of aerospace flights; they should be in suitable form

and easily administered; their toxicity must be low and they must have a

wide therapeutic range of action; they should provide for rapid onset and

long enough duration of expected therapeutic effect; there should be no

deleterious reactions in the residual effects, etc.

It is quite probable that there will be some difficulties in choosing PPA

that would meet all of the above requirements. They can be overcome by

pinpointing exact dosage and time of administration, developing formulas

consisting of products with different pharmacodynamics, etc.

The material published in recent years indicates that some advances have

already been made in this direction. It has been demonstrated in experiments

on animals that PPA may have effects in different directions on resistance

of the organism to specific flight Stressors [11, 12, 17, 22, 38, 44, 72, 90,

and others]. The direction and intensity of the effect are determined by

the spectrum of pharmacological activity of the product, its dosage, time

and route of administration, characteristics of active factor, initial functional state of the organism and a number of other conditions. What is

of basic importance is that one can increase resistance of the organism to

various Stressors by selecting the proper agent and dosage. The above

effect was demonstrated when both stimulant and anxiolytic PPA were studied.

A number of studies conducted on man [14, 20-22, 97 and others] demonstrated

that it is possible to control the body's reactions to flight Stressors:

accelerations, altered gas environment, emotional stress,and fatigue against

the background of prolonged monotonous activity. A remarkable finding made

in the course of the studies is that the same positive results can be obtained by addressing oneself to different elements of physiological regulation using agents with different directions of pharmacodynamics. These

data served as the basis for simultaneous, combined use of various analeptics

and psychostimulants.

In the opinion of some, authors [35, 70, and others], development of combined

products that act simultaneously on various regulator and executor elements

of the organism is a rather promising direction.

A number of authors have tried to combine agents with different pharmacodynamics in order to enhance their activity. For example, in France a

new psychostimulant, debrumil is being advertised [64, 86]; it contains

pyrrolizonecarboyxylic acid, demanol (alleviates'synaptic transmission of

excitation) and heptaminol (cardiovascular analeptic). Robelet and

Lemoine [96] have also proposed a complex psychostimulant; V. S. Shashkov

and N. V. Gordeycheva [582 propose a combination of ephedrine and strychnine;

I. Iordanov [33] reports on the great efficacy of chinoxon, a Bulgarian

combined product, which contains echinopsine base, vitamins Bi and C, and

phytin.

Our studies [22] demonstrated the advantage of a combination of caffeine,

phenamine and strychnine (or securinine) over phenamine alone in the same

dosage as in the formula. The compound stimulant has a stronger effect on
on central nervous system functions according to such criteria as antinarcotic effect stimulation of motor activity, increased resistance to

extreme physical loads, etc. In recents years, efforts are also being made

to combine PPA with stimulant and anxiolytic action in order to normalize

functions of the organs This research was based on observations indicative

of the possibility of obtaining the same positive results with products in

these two groups [28 88, 97, and others]. Furthermore, in his survey Evans

[73] even voices the idea of relativity of making a distinction between

psychostimulant and psychodepressant PPA. Some experimental data can serve

as confirmation of this view. Thus, the studies of Bainbridge [60] showed

that small doses of phenamine have a distinct sedative effect.

Hurst et al. [81] showed that amphetamine has a more potent "antipanic"

effect than an effect of lowering the feeling of tiredness in fatigue.

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Vikhly*yev and T. A. Klygul' [24], V. V. Zakusov

29-32] and other authors demonstrated an activating component in anxiolytics of the benzdiazepine class and their ability to potentiate the

stimulating effects of phenamine.

The combination of psychostimulant and anxiolytic PPA was used in experiments

on animals and studies on man by G. D. Glod et al. [28], B. P. Shestkov [592,

Cuthbertson and Knox 67], Quarton and Talland [94], Rushton and Steinberg

[98], Hurst et al [91], Cooper et al. [67], Quenzer et al. [95] and others.

Simeon et al. [99] and other authors have reported on the use of such

combinations in medical practice. The results of these studies have demonstrated the desirability and potential of this combined approach to

problems of specific regulation of functional state of the organism.

The desirability of combined use of a psychostimulant and anxiolytic can

be illustrated by the results of our research on the antihypoxic activity

of separate and combined use of centedrine and trioxazine, according to

which the antihypoxic activity of the combination is superior to that of

separate use of the ingredients.

Even this brief analysis of the data in the literature illustrates the implications of a search for the ways and means of controlled regulation of function

ot the main physiological systems of the organism in the area of psychopharmacological agents. At this time, apparently only the serious prerequisites

have been formulated for practical implementation of the problems discussed.

Implementation of applied directions of psychopharmacology in aerospace

medicine requires a systems approach, which combines the distinctive features

of physiological, experimental psychological, ergonomic and other investigative methods in the laboratory and under actual conditions of man's

performance. Adoption in practice of scientifically substantiated methods

of psychopharmacological correction of functional state of crew members,

when altered under the influence of separate or combined effects of space

factors and working conditions, will be an important supplement to the existing measures referable to medical back-up of aviation and space flights.

The intensive development of modern psychopharmacology makes it imperative

to pursue continuous and systematic studies both to assess the applicability
of new PPA to aerospace medicine and development of special products with

preset properties.

BIBLIOGRAPHY

1. Aleksandrovskiy, Yu. A. ZH. NEVROPATOL. I PSIKHIATR. [Journal of Neuropathology and Psychiatry], No 12, 1970, pp 1873-1877.

2. Idem, "Clinical Pharmacology of Tranquilizers," doctoral dissertation,

Moscow, 1972.

3. Al'tshuler, R. A., et al. KHIM.-FARM. ZH. [Chemical and Pharmacological

Journal], No 4, 1971, pp 59-62.

4. Al'tshuler, R. A.; Mashkovskiy, M. D.; and Roshchina, L. F. FARMAKOL.

I TOKSIKOL. [Pharmacology and Toxicology], No 1, 1973, pp 18-22.

5. Al'tshuler, R. A.; Roshchina, L. F.; and Mashkovskiy, M. D. Ibid, No ],

1976, pp 9-14.

6. Arbuzov, S. Ya. Ibid, No 6, 1952, pp 46-49.

7. Idem, Ibid, No 5, 1953, pp 13-16.

8. Arbuzov, S. Ya., et al. VOYEN.-MED. ZH. [Military Medical Journal],

No 9, 1965, pp 30-33.

9. Arushanyan, E. B. FARMAKOL. I TOKSIKOL., No 1, 1975, pp 111-120.

10. Bamdas, B. S., 1941. Quoted by Sergeyev, A. A. (No 46).

11. Belay, V. Ye. "Reactivity of the Organism and Drugs Under the Influence

of Accelerations and Altered Gas Environment (Experimental Study),"

doctoral dissertation, Moscow, 1972.

12. Belay, V. Ye.; Vasil'yev, P. V.; and Glod, G. D. KOSMICHESKAYA BIOL.

[Space Biology], No 1, 1970, pp 77-79.

13. Idem, in: "Aviakosmicheskaya meditsina" [Aerospace Medicine], Moscow,

Vol 3, 1971, pp 118-129.

14. Belay, V. Ye.; Glod, G. D.; and Zhiganov, P. I. "Tezisy nauchnykh

soobshcheniy 11-go s"yezda Vsesoyuznogo fiziologicheskogo obshchestva

im. I. P. Pavlova" [Summaries of Scientific Papers Delivered at the 11th

Congress of the All-Union Physiological Society imeni I. P. Pavlov],

Leningrad, Vol 2, 1970, pp 428-429.

15. Berdyshev, V. V. in: "Biokhimicheskiye, farmakologicheskiye i

toksikologicheskiye aspekty issledovaniya adaptatsii" [Biochemical, Pharmacological and Toxicological Aspects of Research on Adaptation],

Novosibirsk, 1967, pp 130-131.
16. Berezhnoy, V. P. VOYEN.-MED. ZH., No 1, 1974, pp 84-87.

17. Brestkina, L. M.; Baryshnikov, I. I.; Gromov, A. Ye.; et al. FARMAKOL.

I TOKSIKOL., No 2, 1975, pp 216-220.

18. Brekhman, I. I. in: "Fiziologicheskiye i klinicheskiye problemy

adaptatsii cheloveka i zhivotnogo k gipertermii, gipoksli i gipodynamii"

[Physiological and Clinical Adaptation of Man and Animals to Hyperthermia,

Hypoxia and Hypodynamia], proceedings of a symposium, Moscow, 1975,

pp 34-35.

19. Val'dman, A. V. VESTN. AMN SSSR [Vestnik of the USSR Academy of

Medical Sciences], No 8, 1975, pp 26-33.

20. Vasil'yev, P. V., et al. KOSMICHESKAYA BIOL., No 3, 1972, pp 53-59.

21. Idem, in: "Kosmicheskaya biologiya i aviakosmicheskaya meditsina"

[Space Biology and Aerospace Medicine], summaries of papers delivered

at the 4th All-Union Conference, Moscow—Kaluga, Vol 1, 1972, pp 9-10.

22. Idem, "Patofiziologicheskiye osnovy aviatsionnoy i kosmicheskoy

farmakologii" [Pathophysiological Bases of Aviation and Space Pharmacology], Moscow, 1971.

23. Vinogradov, M. I., et al. VOYEN.-MED. SB. [Military Medical Collection],

No 1, 1944, pp 39-41.

24. Vikhlyayev, Yu. I., and Klygul', T. A. FARMAKOL. I TOKSIKOL., No 3,

1971, pp 268-269.

25. Vikhriyeva, M. P. "Effects of Minor Tranquilizers on the Emotion of

Fear and Mental Tension in Man (Clinicopharmacological Study)," author

abstract of doctoral dissertation, Sverdlovsk, 1972.

26. Generalov, V. I., et al. VOYEN.-MED. ZH., No 6, 1969, pp 52-54.

27. Ginetsinskiy, A. G.; Samter, Ya. F.; and Natanson, N. V. VOYEN.-MED. SB.,

No 1, 1944, pp 75-80.

28. Glod, G. D., et al. KOSMICHESKAYA BIOL., No 4, 1972, pp 77-83.

29. Zakusov, V. V. FARMAKOL. I TOKSIKOL., No 1, 1971, pp 7-9.

30. Idem, "Pharmacology of Central Synapses," Moscow, 1973.

31. Idem, BYULL. EKSPER. BIOL. [Bulletin of Experimental Biology], No 4,

1973, pp 54-56.

32. Idem, FARMAKOL. I TOKSIKOL., No 4, 1974, pp 389-391.

10
33. Iordanov, I. S"VREMEN. MED. [Modern Medicine], Vol 26, No 2, 1975,

pp 25-27.

34. Kosha, L. VENGERSKAYA FARMAKOTER. [Hungarian Pharmacotherapy], Vol 5,

No 2, 1973, pp 92-95.

35. Kudrin, A. N. in: "Materialy 2-go Vsesoyuznogo s"yezda

farmatsevtov" [Proceedings of 2d Ail-Union Congress of Pharmacists],

Riga, 1974, pp 204-25.

36. Kuz'mich, N. S., et al. VOYEN.-MED. ZH., No 10, 1970, pp 36-39.

37. Kustov, L. A., et al. Ibid, No 12, 1972, pp 56-59.

38. Lavretskaya, E. F.; Voinova, I. I.; and Privol'neva, T. P. KOSMICHESKAYA

BIOL., No 3, 1976, pp 88-89.

39. Lobastov, 0. S.; Spivak, L. I.; and Panov, B. P. VOYEN.-MED. ZH., No 5,

1968, pp 26-29.

40. Mashkovskiy, M. D. "Drugs," Moscow, 1972.

41. Mekhedova, A. Ya., and Luk'yanova, S. N. FARMAK0L. I T0KSIK0L., No 3,

1975, pp 267-269.

42. Patkan, P. in: "Emotsional'nyy stress" [Emotional Stress], Leningrad,

1970, pp 63-66.

43. Roshchina, L. F.; Al'tshuler, R. A.; and Mashkovskiy, M. D. FARMAKOL.

I TOKSIKOL., No 3, 1975, pp 263-267.

44. Rudnev, M. I., and Degtyar', V. N. Ibid, No 5, 1974, pp 552-553.

45. Saratikov, A. S. in: "Stimylyatory tsentral'noy nervnoy sistemy"

[Central Nervous System Stimulants], Tomsk, 1966, pp 3-23.

46. Sergeyev, A. A. "Essays on the History of Aviation Medicine," Moscow—

Leningrad, 1962.

47. Sergeyev, N. P., and Gavrilov, A. S. BYULL. AVIATSION. MED. [Bulletin

of Aviation Medicine], No,3, 1946, pp 26-27.

48. Sereyskiy, M. Ya.' "Nervous System Stimulants," Moscow, 1943.

49. Spivak, L. I. VOYEN.-MED. ZH., No 12, 1972, pp 52-56.

50. Strel'tsov, V. V., and Fedorov, V. I. BYULL. EKSPER. BIOL., No 3,

1955, pp 2-7.

51. Subbotnik, S. 1. VESTN. V0ZDUSHN0G0 FL0TA [Vestnik of the Air Corps],

No 12, 1936, pp 14-15.

11
52. Idem, in: "Voprosy meditsinskogo obespecheniya aviatsii" [Problems of

Medical Support of Aviation], Moscow, Vol 2, 1939, pp 103-109.

53. Idem, BYULL. EKSPER. BIOL., No 6, 1945, pp 49-53.

54. Terakov, I., and Kirov, K. "Clinical Psychopharmacology," Moscow, 1971.

55. Temkov, I.; Tomov, T.; and Kamenov, G. NEVROL. PSIKHIATR. I NEVROKHIR.

[Neurology, Psychiatry and Neurosurgery](Sofia), Vol 14, 1975, pp 179-

183.

56. Trent'yev, V. G., and Khoruzhaya, S. D. VOYEN.-MED. ZH., No 2, 1972,

pp 64-68.

57. Frankenkhoyzer, M. in: "Emotsional'nyy stress," Leningrad, 1970,

pp 24-36.

58. Shashkov, V. S., and Gordeycheva, N. V. KOSMICHESKAYA BIOL., No 2,

1972, pp 3-6.

59. Shestkov, B. P. "Some Psychophysiological Characteristics of an

Operator During Compensatory Tracking," author abstract of candidatorial dissertation, Moscow, 1975.

60. Bainbridge, J. G. PSYCHOPHARMACOLOGIA (Berlin), Vol 18, 1970, pp 314-

319.

61. Berde, B. CHEM. RDSCH. (Switzerland), Vol 28, No 14, Appendix 1, 1975,

PP 3-5.

62. Booth, D. A. NATURE, Vol 217, 1968, pp 869-870.

63. Burstin, S. "Control of Drug Addiction," Buenos Aires, 1963.

64. Caille, E. J. PSYCHOL. MED., Vol 4, 1972, pp 1155-1158.

65. Conners, C. K. PSYCHOPHARMACOLOGIA (Berlin), Vol 19, 1971, pp 329-333.

66. Cooper, S. J.; Daphne, J.; and Summerfield, A. ACTIV. NERV. SUPER.,

Vol 14, 1972, pp 266-268.

67. Cuthberston, D. P., and Knox, J. A. C. J. PHYSIOL. (London), Vol 106,

1947, pp 42-47.

68. Cutting, W. C. "Guide to Drug Hazards in Aviation Medicine,"

Washington, 1962.

69. Davies, B. in: "Advances in Neuropsychopharmacology," 0. Vinar,

Z. Votava and P. Bradley (editors), Prague, 1971, pp 179-183.

12
70. Dengler, H. J., and Lsagna, L. EUROP. J. CLIN. PHARM., Vol 8, 1975,

pp 149-154.

71. Dews, P. B. in: "International Congress on Pharmacology," 6th,

abstracts, Helsinki, 1975, p 404.

72. Domino, E. F.; Albers, J. W.; Potvin, A. R.; Repa, B. S.; et al.

CLIN. PHARMACOL. THER., Vol 13, 1972, pp 251-257.

73. Evans, W. 0. FED. PROC, Vol 29, 1970, pp 1994-1999.

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75. Fox, K. A.; Webster, J. C; and Querriero, F. J. PHARMACOL. RES.

COMMUN., Vol 4, 1972, pp 157-162.

76. Freeman, C. L. J. EXP. PSYCHOL., Vol 26, 1940, pp 602-608.

77. Garattini, S. in: "Abuse of Central Stimulants," Stockholm, 1968,

p 323.

78. Garatiini, S., and Ghetti, V. (editors), "Psychotropic Drugs,"

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79. Holiday, A. R. in: "Drugs and Behavior," L. Uhr et al. (editors),

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80. Hurst, P. M. in: "Psychopharmacology of the Normal Human," W. 0.

Evans and N. S. Kline (editors), Springfield, 1969, p 86.

81. Hurst, P. M.; Radlow, R.; and Bagley, S. K. ERGONOMICS, Vol 13, 1970,

pp 435-444.

82. Joiry, D.; Brunner, H.; and Klein, K. E. "First European Congress on

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83. Lapierre, Y. D. VIE MED. CANAD. FRANC, Vol 3, 1974, pp 605-609.

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13
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1514.

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PP 141-142.

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14
EXPERIMENTAL AND GENERAL THEORETICAL RESEARCH

UDC: 629.78:[611.71-018.4+612.751.1.015.31

CONDITION OF MICROSCOPIC AND CRYSTALLINE STRUCTURES, MICROCONSISTENCY AND

MINERALIZATION OF HUMAN BONE TISSUE FOLLOWING A LONG SPACE FLIGHT

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 11-20

[Article by 0. G. Gazenko, A. A. Prokhochukov, V. V. Panikarovskiy,

R. A. Tigranya, A. G. Kolesnik, G. N. Pakhomov, A. S. Grigor'yan, Z. P.

Antipova, S. M. Remezov and N. A. Komissarova, submitted 22 Jul 76]

[Text] One of the rather pressing and important problems of space biology

and medicine is the state of calcium metabolism in the organism under the

influence of space flight factors. In spite of the advances of modern

space biology and medicine, the problem of calcium metabolism during prolonged space flights is still relatively poorly developed, but it is quite

important from the practical point of view, particularly in connection

with prolonged manned flights on orbital stations.

Elevation of blood calcium content and increased excretion thereof in urine

and feces, decreased mineralization of some skeletal bones (for example, the

calcaneus) have been observed in astronauts who have participated in long

orbital space flights [1-4].

There are a number of unanswered questions in this problem, that are related,

to some extent, to the limited possibility of evaluating mineralization of

bone tissue according to results of roentgenophotometric and ultrasonic

studies, including their crystalline cancellus, protein matrices, proportion of organic and inorganic fractions and other properties that determine

dynamic stability of bone tissue, the mechanism of effects of various space

flight factors, as well as determination of compensatory capabilities of

bone tissue under such conditions.

Methods

Our objective included comprehensive investigation of tissue of different

skeletal bones: calcaneus, femoral epiphysis and diaphysis, body of the

vertebra, rib and sternum (autopsy material from the crew of Salyut-1

station). We used a set of various techniques for more comprehensive and

in-depth examination of this material: pathohistological, crystallographic,

biophysical and biochemical.

15
Figure 1. Compact and spongy bone tissue.

Bone substance; of femoral diaphysis has a compact structure (a), welldeveloped OK tec-mi c structures (b). In the calcaneus there is a predominantly

spongy type of structure; the compact lamella is very poorly developed; the

medullary spaces contain yellow marrow (c); resorption niches and erosions

are demonstrable in the compact lamella without signs of cellular osteoclastic

reaction (d). Hematoxylin-eosin stain; magnification: 40x (a), 125x (b),

55x (c) and 100* (d).

A histopathological study was made of unadulterated [polished] sections,

decalcified and hematoxylin-eosin stained sections of bone tissue. The

crystallographic studies were made by means of x-ray analysis on an URS-50IM

16
roentgenodiffractometer [5]. Microhardness [microconsistency] of bone tissue

samples was determined with a PMT-3 instrument using previously described

techniques [6].

Soft tissues (cartilage, periosteum, marrow) were completely removed from

bone tissue samples, formalin was removed, then lipids and carbohydrates

in order to assay calcium and phosphorus content; we estimated the proportion (percentage) of protein and mineral fractions. Calcium content was

assayed using a flame spectrophotometer and phosphorus with an SF-16 spectrophotometer.

Bone tissue of autopsy material taken from three men who had died of acute

trauma at 20-40 years of age (without pathoanatomically demonstrable signs

of pathology of internal organs and systems) served as the control for

comparative analysis.

In order to obtain data with preset (at least 95%) degree of probability, the

studies were programmed, using mathematical methods [7, 8], with determination

of number of parallel tests and analyses, and other conditions. All of the

obtained digital data were submitted to statistical processing by the method

of Student to determine the degree of reliability.

Results and Discussion

Pathohistological examination revealed structures corresponding to the type

of bone examined in preparations of bone tissue. There were elements of

compact and spongy bone. Well-developed compact bone structures are demonstrable in the femoral diaphysis. In the other bone fragments the compact

substance forms a thin external compact lamella that changes into spongy

bone matter toward the middle. In all preparations, bone is represented by

well-developed osteon structures formed by bone plates concentrically

arranged around blood vessels. Three layers of compact substance are distinct

in the femoral diaphysis: external and internal layers of basic ["general"]

lamellae and a middle osteonic layer. Here and there in the external

layer Volkmann's canals are visible. Mildly basophilic lines are demonstrable

between layers and different osteon systems of the middle layer. The lines

of adhesion in the external layer are parallel to the bone surface and

more intensively stained. The spongy substance of bone also presents osteonic

structure. The Haversian systems of compact and spongy bone contain dilated

plethoric vessels. In some areas over the surface of compact lamellae,

shallow erosions and niches can be seen in the margin of bone trabeculae,

without signs of a cellular osteoclastic reaction (Figure 1).

The medullary lacunae in the spongy substance of the epiphysis and calcaneus

are filled with yellow marrow represented by extremely friable honeycomb-like

substance formed by fat cells, between the well-developed, thick trabeculae.

In the medullary lacunae of the spongy substance of the body of the vertebra,

there are elements of red marrow represented by cells of the myeloid class,

reticular cells, as well as giant cells, i.e., megakaryocytes. Here and

there inclusions of fat cells are seen. The vessels of the yellow and red

17
marrow are dilated and injected with blood. In some preparations there is

significant plethora (Figure 2, a and b).

7'^*V"«JT»"'

V»*, A,

*»

> 'f

Figure 2. Bone marrow and cartilaginous tissue

Medullary Lacunae of rib filled with red marrow (a). Red marrow cells of body

of vertebra represented by elements of the myeloid class; isolated megakaryocytes are encountered (b). The cartilage of the articular surface of the

femoral epiphysis has a structure of the hyalin type (c). There is a mature

cartilage island in the spongy substance of sternal bone tissue (d). Hematoxylin stain; magnification: 40* (a, d) and 125x (b, c).

18
Table 1. Microhardness of bone tissue (kg/cm2

)

Skeletal bone Index

Type of bone tissue

compact | spongy

Calcaneus

SF [space flight]

Normal

Difference [diff.]

kg/cm'1

% of normal

Reliability of diff:

t

P

46,9±0,7

46,3±0,(i

- 0,0

-!-1,3

0,7

>0,05

Epiphysis of

femur

Diaphysis of

femur

Vertebral body

Sternum

Rib

SF

Normal

Diff.:

kg/cm2

% of normal

Reliability of diff,

P

SF

Normal

Diff.:

kg/cm

% of normal

Reliahil.of diff.

P

44,9+0,5

44,1+0.5

i 0,8

i 1,8

1,0

0.00

53,8+0,7

51,0+0,8

1 2,8

5.5

0,05

SF

Normal

Diff.:

kg/cm2

% of normal

Reliabil.of diff.

P

SF

Normal

Diff.: 2

kg/cm

% of normal

Reliabil.of diff,

/

/'

43,0+0,7

40,1+0,0

t 2.5

i 8,7

3,7

---0,01

41,7+0,5

43.0+0,5

•-1,3

- 3,0

1.8

0.05

44,2+0.7

46,5+0,5

—2,3

-4,9

2.G

<r 0,02

SF

Normal

Diff.:

kg/cnr

% of normal

Re 1 Labil.of difJ

/'

50,7+0,5

40,0+0.7

: 4,7

1 10,2

5,3

• ;(),()!

53,9+0,7

5C..2+ f).7

2.3

4.1

2,2

0,'o5

44,4+0,4

42,4+0,0

i 2,0

-I 4,7

2,9

-0,02

39,8+0,0

42,5+0,5

- -2,7

0,1

3,4

. 0.0I

13,0+0,0

39,2-) 0.5

45,0+0.5

40.0+0,5

! 4,1 i 5,0

> 11.2 ! 12,3

' 2 0,7

0,001

Note: Here and in Tables 2-4, SF—space flight.

19
Table 2. Mineral fraction (ash) of bone tissue (% dry weight)

Skeletal bone Index Bone UssiiP

overall I compact SDonev

Calcaneus

SF

Normal

Difference

Reliab.of diff.:

/

P

64,4+0.7

65,5-1-0,6

—1,1

1,2

>0,05

65,0+1,1

65,3+0,8

—0.3

0,2

'X), 05

03,7+0,7

65,7+1,0

—2.0

1,7

>0,05

Epiphysis of

femur

SF

Norual

Diff.

Reliab.of diff.:

t

P

67,8-H),7

68,1+0,8

—0,3

0,3

>0,05

68,2+0,9

69,7+0,2

—1,5

1,7

>0,05

67,5+1,2

66,5+1,5

+ 1,0

0,5

>0,05

Diaphysis of

femur

SF

Normal

Diff.

Reliab.of diff.:

t

P

68,6+1,5

71,4+0,1

—2,8

1.9

>0,05

71,5+0,4 63,3+2,7

Vertebral body

SF

Normal

Diff.

Reliab.of diff.:

t

P

55,9+3,6

52,8+1,1

-1-3,1

1,0

. >o,or>

60,1+0,1

56,1 +1,5

+ 10,0

0,7

'-.-0,00!

57,1 + 1,2

51,2+0,7

+5,9

4,2

•0,001

Sternum

SF

Normal

Diff.

Reliab.of diff . :

t

P

58,6+ 1,8

56,8+2,5

1-1,8

0,6

.: -6,05

64,3+1,5

62,2+0,0

-1-2,1

1.2

•0,05

68,0+0,8

67,6+0,5

-1-0,4

0,4

; 0,05

53,4+0,7

51,4+1,5

-12,0

1,2

'.:. 0,05 '

Rib

f SF

Normal

Diff.

Reliab.of diff.:

P

63,7+2,5

64,1+2,1

—0.7

0,2

; -0,05

53,6+4,3

55,0+1,6

— 1,4

0,3

; 0.05

Cartilaginous tissue is demonstrable in preparations of femoral epiphysis.

The localization of the cartilage corresponds to the articular surface of

the bone. Structurally, the cartilage is of the hialine type. The cartilaginous cells are diverse in shape, mainly oval, and elongated only near the

cartilage surface. The intercellular substance is amorphous and markedly

basophilic (Figure 2c).

fn one of the histological preparations of sternal tissue, islands of mature

cartilage varying in size are demonstrable in the spongy substance of the

manubrium, which is often intimately related to the substance of the

osseous trabeculae. At the same time, some parts of this cartilage

20
present dystrophic changes and it is invaded by capillary type blood vessels;

the impression is gained that there is enchondral replacement of cartilage

with osseous structures (Figure 2d).

Table 3. Calcium content of bone tissue (% of ash)

Skeletal bone

Calcaneus

Epiphysis of

femur

Diaphysis of

femur

Vertebral body

Sternum

Index

overall

SF

Normal

Difference

Reliab.of diff.

t

P

Bone tissue

36,1 ±0,1

36,1 ±0,1

0

0

>0,9

Rib

SF

Normal

Diff.

Reliab.of diff

t

P

SF

Normal

tiäb.of diff.

«Ulli..

Diff,

Reli

t

P

37,1 ±0,1

36,7±0,1

-

L

0,4

0,2

>0,8

compact

36,7±0,3

35,4±0,2

-7-1,3

0,8

>0,4

SF

Normal

Diff.

Reliab.of diff

P

36,6±0,2

35,4+0,1

+ 1,2

6,0

<ro.ooi

SF

Normal

Diff.

Reliab.of diff

/'

SF

Normal

Diff.

Reliab.of diff

/

35,8+0,3

36,1+0,1

—0,3

1.0

; -0,3

36,0+0,2

35,2+0,2

10.8

2,9

ro.oi

35,5+0,1

36,0+0,2

—5,5

2,6

<'0,02

37,2+0,2

36,5+0,1

4-0,7

1,3

>0,1

37,3±0,6

34,6+0,1

+2,7

4,7

<0,001

35,8+0,1

30,4+0,4

—0,6

1,2

•0,1

36,3+0,3

36,2+0,1

; o.!

0,6

:>5,8+0,3

35,6+0,2

-• 0,2

0,6

".. 0.5

suonav

35,5+0,1

36,2+0,2

+0,3

1,4

->o.i

37,0±0,2

36,9+0,1

+0,1

0,1

>0.9

35,5+0,5

36,1+0,3

--0,6

1,0

.• 0,3

36,6-1-0,1

34,2+0,5

12,4

1,2

"' -0.2

The external layer of bone fragments is covered with periosteum, which consists of two layers: fibrous and adventitial. There are blood vessels and

osteoblasts in the internal layer. The external layer of periosteum consists

of compact connective tissue containing coarse bundles of collagen fibers.

Blood vessels traverse this layer also. Thus, the described histological

findings correspond to variants of microscopic structure of normal human

skeletal bones.

2.1
Table 4. Phosphorus content of bone tissue (% of ash)

Skeletal bone Index Bone tissue,

overall compact

Calcaneus

Epiphysis of

femur

Diaphysis of

femur

SF

Normal

Difference

Reliab.of diff.

i

P

SF

Normal

Diff.

Reliab.of diff,

t

P

16,4±0,1

15.6±0,1

+0,8

7,9

<0,001

16,4±0,1

15,94-0,2

4-0,5

2,5

<0,02

spongy

1G,0±0,1

16,1±0,2

—0,1

0,5

>0,G

I6,4±0,l

15,0±0,1

4-1,4

10,0

<0,001

1(1,44-0,1

16,1+0,2

-I 0,3

0,1

>0,9

SF

Normal

Diff.

Reliab.of diff,

t

P

16,54-0,1

15,04-0,1

4-1,5

12,0

<0,()01

Vertebral body

Sternum

SF

Normal

Diff.

Reliab.of diff.:

t

P

Rib

SF

Reliab.of diff,

/

P

SF

Normal

Diff.

Reliab.of diff,

t

P

10,6+0,1

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-! 2,0

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0,001

10,1

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H 1,0

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:0.02

10,840,';

14,94-0,1

-] 1.9

«,2

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16,04-0,1

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<0,001

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15,7+0,3

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Crystallographic studies, based on interpretation of roentgenodiffractograms

19J revealed that the interplanar distances correspond to a mixture of

hydroxylapatite, fluorapatite, tricalcium phosphate, etc., in the examined

specimens of calcaneal bones following a space flight. Nevertheless, in

these samples, there are more distinct (as compared to normal) lines that

are typical for hydroxylapatite, carboyslapatite and tricalcium phosphate.

This is indicative of more marked crystallization than in control samples.

The interplanar distances, as well as parameters of elementary cell of apatite

crystals, are very similar in values. For this reason, the lines of interplanar distances are overlapped on the roentgenodiffractograms, so that we

cannot clear.1 y determine whether there is prevalence of any type of apatite.

22
Thus, the delineation of crystalline structures of bone tissue in the group

under study is somewhat greater than in the control group. According to

the studied parameters of the crystalline structure, it can be considered

that there are more active processes of crystallization in bone tissue of

the group in question than in the control group.

Analysis of microhardness of normal bone tissue (control group) revealed

that the microhardness levels are the same for compact and spongy bones of

all skeletal bones studied (with the exception of the femoral diaphysis),

and there are no appreciably reliable differences. Microhardness of the

diaphysis of the femur (both compact and spongy parts) is an average of

12.5% greater than in other skeletal bones. These data are consistent with

the literature [10].

A comparison of microhardness of bone tissue in the studied and control

groups failed to demonstrate substantial differences. The existing differences between microhardness indices of homologous bones in the studied and

control groups fluctuate over a few percentage points, which could be attributed to individual variability and permissible range of error of the

methods used (Table 1). The demonstrated statistically reliably and

substantial differences, in the direction of increased microhardness of some

bones, for example the femoral epiphysis, rib and others, can apparently be

interpreted as some increase in strength of these bones, related for example

to intensive physical training, accelerations, etc., which do not have an

appreciable effect on their function.

The mineral fraction of bone tissue (both compact and spongy), as well as

proportion thereof in relation to the protein fraction, did not differ

appreciably from normal (control group) in all bones examined. In the

test group, there was some elevation (by 5.9-10.0%) of mineral content in

the vertebral body, as compared to normal (Table 2).

A study of calcium content failed to demonstrate differences from normal

in any of the bones examined. There are statistically reliable deviations,

in the range of 0.5-0.8-1.2-2.70, as compared to normal, which can be interpreted as individual fluctuations, as well as permissible error factor of

the method (Table 3).

A study of phosphorus content of bone tissue revealed differences, in the

direction of 0.5-2.0% increase, as compared to normal, and there was a

rather high degree of reliability in a number of cases (99.99%; Table 4).

Comparative analysis of the results of these comprehensive studies of bone

tissue of the human skeleton following a prolonged space flight, using

various methods, demonstrated a clearcut correlation according to the indices

studied. Pathohistological studies and x-ray analysis revealed that the

microscopic and crystalline structures of bone tissue in all skeletal bones

examined do not differ from normal (control group). There was also a distinct

consistency between indices of microhardness and mineralization (ash, calcium

and phosphorus) of skeletal bone tissue, which are within the normal range.

23
No appreciable deviations from normal that could have been interpreted as

pathological were demonstrable according to all parameters studied. The

changes in the direction of consolidation of the crystalline lattice of

bone tissue, increased microhardness and mineralization can most likely be

attributed to the effect of physical loads and training [conditioning]. On

the basis of analysis of the literature and results of these studies it

is difficult to derive a definite conclusion to explain the substance

of the data obtained at this time. For this reason, we shall merely

expound an assumption (as a working hypothesis) that the normal condition

of bone tissue of the human skeleton following a prolonged space flight

could be due to a high level of physical training and conditioning of astronauts and subsequent use of the set of equipment and conditioning measures

onboard the Salyut-1 orbital station, that were directed toward precluding

the undesirable effects of weightlessness and hypokinesia on the human body

during orbital space flights.

BIBLIOGRAPHY

1. Biryukov, Ye. N., and Krasnykh, K. G. KOSMICHESKAYA BIOL. [Space Biology],

No 6, 1970, pp 42-46.

2. Berry, Ch. AEROSPACE MED., Vol 41, 1970, pp 500-519.

3. Hatter, R. S., and McMillan, D. E. Ibid, Vol 39, 1968, pp 849-855.

4. Vogel, D., and whiffe, S. L. in: "Skylab Life Sciences Symposium.

Proceedings NASA," Houston Vol 1, 1974, pp 387-400.

5. Pakhomov, G. N. IZV. AN LATVIYSK. SSR [News of the Latvian Academy of

Sciences], No 3, 1968, pp 147-149.

6. Remezov, S. M. STOMATOLOGIYA [Stomatology], No 3, 1965, pp 33-37.

7. Urbakh, V. Yu. "Biometrie Methods," Moscow, 1964.

8. Hicks, C. "Basic Principles Involved in Planning Experiments," Moscow,

1967.

9. Giller, Ya. L. "Tables of Interplanar Distances," Moscow, 1966.

10. Panikarovskiy, V. V.; Prokhonchukov, A. A.; Grigor'yan, A. S.; et al.

ORTOPED. TRAVMATOL. [Orthopedics and Traumatology], No 12, 1974, pp 48-60.

24
UDC: 629.78:[612.13+612.18

DISTINCTIVE FEATURES OF REGIONAL CIRCULATION AND VASOMOTQR REGULATION

FOLLOWING A TWO-MONTH SPACE FLIGHT

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 20-26

[Article by Kh. Kh. Yarullin and T. D. Vasil'yeva, submitted 26 Apr 76]

[Text] Redistribution of blood in the body is one of the main mechanisms

of regulation of adequate blood supply to organs and tissues. In the presence

of regional circulatory disorders, for example in the brain, there is also

redistribution of blood in different vascular reservoirs, to compensate for

the hemodynamic changes and to maintain homeostasis. It is particularly

interesting to study vasomotor regulation and regional hemodynamics of

astronauts during and after space flights in view of the significant redistribution of blood in the body under the influence of weightlessness. In

this report, we submit the results of rheographic investigation of regional

hemodynamics in the crew of Soyuz-18 and Salyut-4 before and after a 2-month

orbital flight.

Method

During passive orthostatic and antiorthostatic tests we recorded synchronously

rheoencephalograms (REG) in the frontomastoidal and bimastoidal leads, which

reflects pulsed flow [filling], elasticity and tonus of vessels m the

system of the internal carotid artery and vertebrobasilar system, as well as

rheograms (RG) of the right lung and crus, photoplethysmogram (PPG) of the

third finger and EKG in the second standard lead. Under basal metabolic

conditions, we also tested RG of the liver, forearm, fingers and toes.

Studies under basal metabolic conditions were pursued before the flight and

on the 1st, 3d, 16th and 40th (59th) days after landing. The method used

to analyze the RG was described previously [7]. The orthostatic test was

performed with the table turned at an angle of +70° for 10 min, and the

antiorthostatic one, at angles of -15° and 30° for 6 min. The orthostatic

and antiorthostatic tests were performed once before the flight, on the 1st,

3d, 7th, 14th and 40th (56th) postflight days.

25
Results and Discussion

The rheographic studies under basal metabolic conditions revealed more or

less marked changes in regional hemodynamics both after the 2-month and

1-month orbital flights. On the 1st postflight day, P. I. Klimuk presented

distinctly lower tonus of arterioles and veins in the system of the internal

carotid: as compared to preflight values, there was a 23.6-28% decline of

dicrotic (DCI) and diastolic (DSI) indices of the REG. The diminished vascular tonus was associated with 20% decrease in pulsed filling of the left

hemisphere. In the vertebrobasilar system arteriolar and venous tonus was

increased to the normal level and there was some increase in pulsed filling.

In V. I. Sevast'yanov, we observed diminished tonus of arterioles and veins

in the right hemisphere (DCI of hemispheric REG dropped from 51.5 to 21.2%;

DSI, from 54.6 to 17.5%) and vertebrobasilar system (DCI of occipitomastoidal

REG dropped from 36.3 to 18.7%, and DSI, from 41.1 to.21.4%) with minor

decrease in vascular tonus of the left hemisphere. Pulsed filling of cerebral

vessels in all three reservoirs studied, as well as of the lung and finger,

was significantly increased (by 60-100%, particularly in the left hemisphere).

As we see, both cosmonauts presented distinctly asymmetrical pulsed filling

and cerebrovascular hypotension. Yet, on the 1st day after a 1-month flight,

A. A. Gubarev and G. M. Grechko presented increased tonus of cerebral arterioles and veins (DCI of REG rose to 91.5-100% and DSE, to 103.5-110%). The

preflight DCI and DSI did not exceed 44.3 and 33.%, respectively, in the

former cosmonaut and 77.5 and 87.6%, in the latter. In other words, both

cosmonauts presented signs of cerebrovascular, particularly venous, i.e.,

postcapillary hypertension [1, 4, 15, 17]. There was also prevalence of

signs of venous hypertension in the lungs and liver of G. M. Grechko, venous

and arteriolar hypotension in the liver and crus of A. A. Gubarev.

In P. I. Klimuk and V. I. Sevast'yanov, the signs of vascular hypotension

of the leg and toes, particularly venous, were much less marked, in spite

of their 2-month flight, than in A. A. Gubarev and G. M. Grechko. Thereafter,

the indices of tonus of precapillary and postcapillary vessels of the crus

came close to preflight levels as early as the 17th day of the readaptation

period in the crew of the second expedition, whereas in the crew of the

first expedition these indices remained overtly low, even on the 30th day.

At the same time signs of deposition of blood in the lungs and liver were

more marked in P. I. Klimuk and V. I. Sevast'yanov.

Apparently the sharp increase in pulsed filling of the finger after the

flight, against the background of significant increase in vascular tonus,

in A. A. Gubarev and G. M. Grechko is due not only to redistribution of

blood, but entrance of tissular fluid into the capillary stream. The

relative prevalence of vasodilatation could have induced increase exit of

fluid from capillaries [4, 17], which was observed in P. I. Klimuk and V. I.

Sevast'yanov. The demonstrated difference in mechanisms of increasing

blood supply to the finger is apparently due to successful adjustment of

changes in fluid and sodium metabolism which occurred during the 2-month

flight of P. I. Klimuk and V. I. Sevast'yanov and succeeded in effectively

normalizing vasculartonus and capillary circulation, i.e, the microcirculatory system [2, 12, 17].

26
+50

0

-so

1

2 %

I i

+50

n

1

-SO L

\V.4

- Vi i

+50 -

0

- y

_ """/^

-50

i i

+50

^+70J

Background

+70J

1st

i

+

70y «_j «_j *?0^ ^ «_j *77^ «,_,

3d 7th 58tn days

Figure 1. Dynamics of changes in maximum amplitude (1), dicrotic (2)

and diastolic (3) indices of bimastoidal REG in P. I.

Klimuk during orthostatic test before and after 2-month

flight (%)

The prevalence of vasoconstrictive reactions in A. A. Gubarev and G. M.

Grechko for the first 3 postflight days could be attributed, to some extent,

to adaptive increase in tonus of peripheral vessels, which aided in maintaining adequate circulation in the presence of a decreased circulating

blood volume [13]. The effective correction of changes in fluid and sodium

metabolism of P. I. Klimuk and V. I. Sevast"yanov at the end of the flight

was instrumental in some degree of restoration of circulating blood volume

and, consequently, predominance of vasodilator reactions. Asymmetry of

vascular tonus of the hemispheres in V. I. Sevast'yanov and P. I. Klimuk could

have been due to either individual distinctions of vascular tonus and

reactivity or development of vegetovascular dysfunction, i.e., more or less

marked change in function of vasomotor centers. The changes in vascular

reactivity and tonus could have been induced, particularly during the

antiorthostatic test, by the direct effect of fluctuations of intracranial

pressure on hypothalamic and stem vegetative elements that regulate vascular

tonus.

The most marked changes in cerebrovascular reaction to postural factors were

demonstrable in P. I. Klimuk on the 1st postflight data. As can be seen in

Figure 1, the orthostatic test was associated with a drop of DCI (by 81%) and

DSI (by 60%) on the bimastoidal REG. Signs of arteriolar and venous hypotension in the vertebrobasilar system were associated with weakness, vertigo,

as well as nausea, particularly when turning and bending the head. Signs

of difficult efflux and venous stasis were demonstrated on the RG of the

lower leg. In spite of this, the entire test was performed. Evidently,

concurrent compensatory increase in pulsed filling of the internal carotid

(by 36.8%) aided in maintaining the critical level of blood supply to the

brain, for which reason there was satisfactory endurance of the test.

At the same time, in cosmonaut A. A. Gubarev, a similar decrease in vascular

tonus, particularly arteriolar, in the vertebrobasilar system was associated

with appreciable decrease in pulsed delivery of blood to the brain (Figure 2).

27
Already in the 1st min of being in vertical position, there was a decrease in

arteriolar tonus, both in the hemispheres and vertebrobasilar system (DCI

dropped from 85.2 to 10-11.5% and DSI, from 83.3 to 47.5-27.4%), and this

was associated with 32.5% decrease in pulsed delivery of blood. Hypotension

of cerebral vessels and arterioloparesis were associated, from the 4th min on,

with very rapid elevation and sharp decline of REG wave, with increase in its

amplitude. Evidently, the cerebral vessels, having lost their elasticity

and capacity to contract, reacted passively to the fluctuations of systemic

arterial pressure. All this was associated with weakness, mild nausea and

profuse cold perspiration, i.e., development of a precollaptoid state. For

this reason, the table was moved to horizontal position after 4 min and 15 s.

AMAVWAA-AAA^-AA^ A4V~AAAA-A^

^XJIJUL^JLJI C^-^~JLJU-

A^V

~WVVJW/VA/U_/Y.

Figure 2. Dynamics of frontomastoidal (1) and bimastoidal (3) REG,

derivatives of hemispheric REG on the right (2) and RG of

the lung (6); photoplethysmogram of the finger (4), RG of

right lung (5) and lower leg (7), and EKG (8) of A. A.

Gubarev before and during orthostatic test on 1st postflight

day.

A) background tracing in horizontal position D) 5th min of vertical position

B) 1st min of vertical position E) recovery period in

C) 3d min horizontal position

28
In P.I. Klimuk, the vertebrobasilar system was found to be less resistant

to antiorthostasis as well on the 1st postflight day (Figure 3). Compensatory

increase in arterioral tonus of this system was less marked than before the

flight, while venous tonus even diminished, and this was associated with

passive increase in pulsed delivery of blood (by 172% at -15° angle and 260%

at -30°; 73.2 and 100%, respectively, before the flight), i.e., development

of subcompensated venous stasis. More marked passive cerebral hyperemia

during antiorthostasis on the 1st postflight day is indicative of local impairment of autoregulation of hemodynamics in the vertebrobasilar system.

250

200

150 -

WO 1

21 .X.

+ 50 jj/ <

0 I

-25

l .....J

250 -

-15°j -30"\

250

200

150

WO

250

200

150

WO

-P-*S up -sop

Background 1st 3d 7th 58th days

Figure 3. Dynamics of changes in maximum amplitude (1), dicrotic (2)

and diastolic (3) indices of bimastoidal REG of P. I.

Klimuk during antiorthostatic load before and after

2-month flight (%)

Since worsening of well-being of P. I. Klimuk and A. A. Gubarev during the.

orthostatic test was preceded by a decrease in tonus of arterioles and veins

in the vertebrobasilar system, there is reason to believe that impairment of

autoregulation of hemodynamics in this reservoir Is one of the triggering

mechanisms of decreased orthostatic stability. The possibility cannot be

ruled out that the vestibular disorders observed in P. I. Klimuk during and

after the flight are related to the above-described hemodynamic disturbances

in the vertebrobasilar system. It is known that even minor changes in

blood pressure or decreased flow of blood in the internal auditory arteries,

which are branches of the basilar artery, can induce vestibular disorders

[16]. Furthermore, P. I. Klimuk presented signs of arteriolar and venous

hypotension in the vertebrobasilar system following an 8-day flight as well.

In V. I. Sevast'yanov, orthostasis on the 1st postflight day was associated

with decrease in pulsed delivery of blood (by 48.5%) and in tonus of cerebral

29
arterioles and veins, which was more marked in the reservoir of the internal

carotid (DCI and DSI of hemisphere REG diminished by 32%). The 433% elevation of diastolic index of the RG of the lower leg during the orthostatic

test on the 1st postflight day was indicative of plethora of the veins,

apparently due to diminished elasticity and tonus of deep veins of the crus

[9, 11]. This elicited a sharp compensatory increase of arteriolar tonus

and restricted arterial influx to a greater extent than before the flight.

Consequently, orthostatic endurance was also diminished in V. I. Sevast'yanov,

but to a lesser extent than in P. I. Klimuk. In both cosmonauts, signs of

plethora of the brain during the antiorthostatic test were appreciably more

marked than before the flight. In the crew of Soyuz-17 and Salyut-4, on the

1st postflight day considerably less increase in cerebral filling was noted

in antiorthostasis than before the flight, whereas in the vertebrobasilar

system there were fewer or no changes against the background of distinctly

increased arteriolar and venous tonus. These residual compensatory reactions

of cerebral hemodynamics gradually disappeared by the 7th postflight day in

A. A. Gubarev and G. I. Grechko. With repetition of antiorthostatic tests,

there was improved tolerance of the tests by P. I. Klimuk and V. I.

Sevast'yanov. This was manifested by a lesser increment of pulsed delivery

of blood, against the background of marked compensatory increase in tonus

of cerebral vessels, which limited passive cerebral hyperemia in antiorthostatic position. The manifestations of adaptation of cerebral vessels

toward the 2d month of weightlessness were the most marked on the 16th postflight day and leveled off by the 40th day. Endurance of orthostatic position gradually improved in both cosmonauts and was close to the preflight

level on the 16th day of the readaptation period.

There was less change in a/T (%) (tonus index, mainly of large and medium

caliber vessels) under the influence of postural factors, as well as at

rest, than in DCI and DSI; not infrequently it presented minimal changes.

It rose reliably only with a sharp decrease of tonus of cerebral arterioles

and veins during antiorthostasis. Apparently this increase in tonus of

arteries of large caliber was compensatory and directed toward providing

hemodynamic homeostasis in the presence of significant decrease in arteriolar

and venous tonus.

On the 30th postflight day, DCI and DSI remained low on the RG of the leg

and PPG of the finger of A. A. Gubarev and G. M. Grechko. Since the DCI

reflected the state of precapillary fine vessels and DSI, that of postcapillary ones [1, 3, 5, 6, 8, 10, 14, 17] the above signs of arterial and

venous hypotension were indicative of microcirculatory changes, particularly

in regions with less capacity for self-regulation.

At the same time, the results of rheographic studies of regional hemodynamics

during postural tests demonstrated weakening of mechanisms of self-regulation

of cerebral circulation for the first 3 days after returning to earth. This

was manifested by diminished orthostatic stability and even development of

collapse in A. A. Gubarev at the very start of the orthostatic test, as a

result of diminished tonus of cerebral vessels, particularly arterioles, and

signs of vasoparesis, mainly in the vertebrobasilar system which was also

30
less stable before the flight. As a result, arterial ischemia of the brain

was complicated by circulatory venous ischemia and led to decompensation of

self-regulation of cerebral blood flow and of the cardiovascular system as a

whole. Since a decline of DCI on the PPG of the finger, from 86% to 0,

against the background of minor decline of DSI (from 86 to 62%), preceded

development of the presyncopic state, it can be assumed, with a high degree

of probability, that the significant decrease in tonus and contractility

of fine precapillary vessels, i.e., arterioles and precapillaries, is one

of the mechanisms of development of orthostatic hypotension, since the tonus

of fine postcapillary vessels remained rather high.

The prolonged persistence of sequelae of adaptation of cerebral vessels to

stress factors related to weightlessness is indicative of the fact that a new

stable state of cerebral hemodynamic homeostasis was obtained by the end of

the 2-month flight.

BIBLIOGRAPHY

1. Mukhamedrakhimov, F. F. EKSPER. KHIR. [Experimental Surgery], No 8,

1966, pp 10-13.

2. Mchedlishvili, G. I. "Function of Cerebrovascular Mechanisms,"

Leningrad, 1968.

3. Pressman, L. P. "Clinical Sphygmography," Moscow, 1974.

4. Chernukh, A. M.; Aleksandrov, P. N.; and Alekseyev, 0. V. "Microcirculation," Moscow, 1975.

5. Eninya, G. I. "Rheography as a Method of Evaluating Cerebral Circulation,"'Riga, 1973.

6. Yarullin, Kh. Kh. in: "Klinicheskaya neyrofiziologiya" [Clinical

Neurophysiology], Leningrad, 1972, pp 544-559.

7. Yarullin, Kh. Kh.; Krupina, T. N.; and Vasil'yeva, T. D.

KOSMICHESKAYA BIOL. [Space Biology], No 4, 1972, pp 33-39.

8. Allison, R. D. J. AM. GERIATR. SOC, Vol 16, 1968, pp 39-51.

9. Dietlein, L. F. in: "The Skylab Life Sciences Symposium Proceedings,"

Houston, Vol 1, 1974, pp 369-388.

10. Donzelot, E.; Milovanovich, J.; and Meyer-Heine, A. ARCH. MAL. COEUR,

Vol 11, 1950, pp 1013-1016.

1L. Thornton, W. E.; Hoffer, G. W.; and Rummel, J. A. in: "The Skylab Life

Sciences Symposium Proceedings," Houston, Vol 2, 1974, pp 197-209.

31
12. Fulton, G. P. ANGIOLOGY, Vol 3, 1957, pp 101-104.

13. Hunziker, 0.; Emmegger, H.; Frey, H.; et al. ACTA NEUROPATH. (Berlin),

Vol 29, 1974, pp 57-67.

14. Meyer-Heine, A.; Giblin, S.; and Desertenne, G. ARCH. MAL. COEUR,

Vol 42, 1949, pp 337-351.

15. Moniz de Bettencourt, J. BOLL. SOC. ITAL. CARDIOI,., Vol 15, 1972

pp 807-810.

16. Toole, J. F., and Patel, N. N. "Cerebrovascular Disorders," New York,

1967.

17. Zweifach, B. W. ANN. REV. PHYSI0L., Vol 35, 1973, p 117.

32
UDC: 612.13-06:612-087.5:616-001.12-031.

22-092.6

STUDIES OF CIRCULATION DURING LBNP TEST ABOARD SALYUT-4 ORBITAL STATION

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 26-31

[Article by V. A. Degtyarev, V. G. Doroshev, T. V. Batenchuk-Tusko,

Z. A. Kirillova, N. A. Lapshina, S. I. Ponamarev and V. N. Ragozin,

submitted 21 Sep 76]

[Text] The functional test using lower body negative pressure (LBNP) is

used constantly in the system of medical monitoring of astronauts [1, 2].

Studies conducted during preflight preparations [3, 4] and in weightlessness

[5] confirmed that this test is informative in determining orthostatic endurance of the crews. However, there are still some problems to be solved:

mangitude of decompression used, frequency of tests, distinctions of circulatory reactions to LBNP in weightlessnes, criteria of endurance thereof,

etc.

The functional test with LBNP was conducted on the Salyut-4 orbital station

in order to evaluate and predict orthostatic endurance of cosmonauts.

Methods

LBNP tests were conducted three times in the preflight period: 94, 67 and

8 days before the flight.

During the flight on Salyut-4 orbital research station, P. I. Klimuk performed the test 9 times (on the 14th, 18th, 22d, 28th, 31st, 37th, 44th,

53d and 60th days) and V. I. Sevast'yanov, 10 times (19th,=14th, 22d, 27th,

31st, 37th, 43d, 53d, 60th and 61st days).

A comprehensive study of circulation with LBNP was conducted five times on

each cosmonaut. After landing, the test was made in 6 h (0 day), 4th and

6th days. LBNP was created by immersing the subject in a Chibis pressure

suit. For the first 2 min of the test, pressure was lowered by 25 mm Hg, in

relation to ambient level, and by 35 mm Hg in the next 3 min. Before,

during the test and during the recovery period, we recorded the tachyosclllogram (TO) and distal perimetric oscillogram (DPO) of the brachial

artery, kinetocardiogram (KKG) in the region of the apex beat and

33
sphygmogram of the femoral artery (SPG). We measured the rate of cardiac

contractions, arterial pressure, velocity of pulse wave (PWV) in the aorta,

phases of cardiac cycle in the left ventricle. We calculated stroke and

minute blood volumes, specific actual and standard [proper] peripheral

resistance of vessels.

The inflight data were compared to all preflight test results, but the

graphs included results of a test made 8 days before the flight, since it

was conducted in the same climate zone and under the same conditions as

the postflight studies.

Results and Discussion

The cosmonauts had no complaints during LBNP; their heart rate increased

by 30-36%, minute volume decreased by 20-37% and stroke volume by 33-45%.

Diastolic arterial pressure rose by a maximum of 11-18%, while pulse

pressure rose by 20-26%. Mean dynamic pressure showed virtually no change

(±8%). PWV of the aorta slowed down somewhat during the test on P. I.

Klimuk but did not change in V. I. Sevast'yanov.

Ejection time and mechanical systole diminished by 10-16% in P. I. Klimuk

and 25-23% in V. I. Sevast'yanov. The phase of isovolumetric contraction

was 17% longer in the former and showed virtually no change in the latter.

The interphase coefficient K [5] increased by 28-30%. In addition to

general changes inherent in all tests with LBNP, each of them presented its

own distinctions. Apparently, best endurance of LBNP by the commander was

observed on the 94th and 67th preflight days. According to hemodynamic

indices, optimum endurance was referable to the first test in V. I.

Sevast'yanov, and the reaction to the second test was more marked. P. I.

Klimuk presented the greatest increment of heart rate, 31-36%, in the

LBNP test 8 days before lift-off. There was a more distinct decrease of

stroke and minute volumes, by 32-33%. In V. I. Sevast'yanov, at the last

test the maximum increase in heart rate constituted 23-30%. Stroke and

minute volumes decreased by 32-36% and 8-17%, respectively.

According to the reports of V. I. Sevast'yanov, LBNP was better tolerated

in weightlessness than before the flight. P. I. Klimuk did not observe any

appreciable difference in weightlessness. According to the results of

inflight tests, there were more marked changes in stroke and minute volumes,

and peripheral resistance of vessels. The arterial pressure reaction did

not differ from the preflight level, and PWV in the aorta increased. There

were greater changes in phase structure of the cardiac cycle: 70-80% elevation of interphase index in P. I. Klimuk and 40-50% in V. I. Sevast'yanov.

In P. I. Klimuk, stroke volume showed a maximum drop of 50-53% and minute

volume, 37-38% (14th-31st day). On the 14th day, we also observed the

maximum increase in heart rate, by 40%. The test performed on the 37th day

resembled the second preflight test, which was rated as best with regard to

endurance. The reaction to LBNP in flight was stable in V. I. Sevast'yanov.

The stroke volume dropped to 34-45% and minute volume, to 25-35% in the

tests on the 22d, 31st and 37th days. These changes resembled the results

34
of the second preflight test, in which there were maximum deviations of most

hemodynamic indices.

With LBNP, increment of actual peripheral resistance in V. I. Sevast'yanov

constituted 56-38% on the 22d-31st day and only 24% on the 37th day. The

LBNP test on the 53d day was performed against the background of a fluid and

sodium load. In P. I. Klimuk, the hemodynamic changes resembled the circulatory reaction with LBNP on the 14th day. In V. I. Sevast'yanov, they were

about the same as on the 22d and 37th days.

We examined the dynamics of cardiac contractions and phases of the. cardiac

cycle with LBNP on the 60th and 61st days. These data did not differ appreciably from those obtained at earlier stages of the flight. Postflight

LBNP tests were considered more difficult by the cosmonauts than preflight

and inflight ones. The first postflight test elicited maximum hemodynamic

changes in P. I. Klimuk. During LBNP against the backgrouhd of a high

initial pulse rate, pulse pressure dropped by 37-45%, stroke volume, by

45-50% and minute volume, by 35%. Maximum increment constituted 40%. In

our opinion, the increased minute volume toward the end of the test, in the

presence of tachycardia throughout the test, was an adverse sign. The

reaction to LBNP on the 4th and particularly 6th days did not differ

essentially from the 1st and 2d preflight tests, which is indicative of

rapid recovery of orthostatic stability in P. I. Klimuk (Figure 1).

1234S /2>23\l2 !2I23\1

LBNP Recov. LBNP Rec . LBNP

-8 day 14 day 22 d.

A^ " ,*-*-v 1

a/—•4^

\t/

1 I 1 1 la i. i 111111111 (

I2l23\l23 / 2 1 23\l2 I 23

LBNP Rec.LBNP- Rec.

31 day 37 d.

/ min

Recovery

I 2 f 2 3

LBNP

53 day

fluid £

sodium load

12 12 3 l\2J4 S

LBNP Rec.

H-0 day

Figure 1

12 12 3!

LBNP

34 5 I 2 ! 2 3\l 2 3 4 5 min

Rec. LBNP Recovery

+4 day +6 day

Hemodynamic changes in P. I Klimuk during LBNP in the

preflight period, during mission and postflight period

a) pulse white columns—stroke volume

O) specific actual resistance black columns—minute volume

e) pulse pressure

35
Endurance of LBNP was somewhat better 6 h after the mission in V I

Sevast'yanov than P. I. Klimu. On the 4th day, the test was associated with

the least hemodynamic changes and, apparently, it was the best. On the 6th

day, orthostatic stability diminished. The test resembled the second post-

„»? t6St °

n P

'

I

'

Klimuk; however, a significant decrease of stroke (by

53/) and minute (45%) volumes was noted only in the 1st min of the test;

there was less change in the indices thereafter. After equalization of'

pressure in the [pressure] suit, cardiac output and pulse pressure increased

by 38-55% (Figure 2). During the same test, there was a marked change in

phases of the cardiac cycle: the interphase index reached 160%.

\r 2 3 4 smtii 2 r 2 3 \ i ? min

Recov. LBNt itecov.

22 day

' 2 1 2 3\1 2 fflin

LBNP Recov

31 day

—t—L-J I L_ 1_

/ 2 t 2 3\i 2 3 min

. LBNP Recovery

37 day

LBNP

/ 2 1 2 3]/ 2 3 4 Sain

fluid L3NP Recov.

fSa^ 0 day

12 i 2 3\i2 jmin

LBNP Recov

Figure 2,

2 1 23\l2345 min

LBNP Recov.

+4 day +6 day

Changes in hemodynamic indices of V. I. Sevast'yanov during

LBNP test in the preflight, inflight and postflight periods

Key is the same as for Figure 1.

Thus, the reaction to the functional test with LBNP in weightlessness was

in the same direction as on earth with regard to most indices. However,

the more significant change in stroke and minute volumes and velocity of

pulse wave, as well as duration of phases of cardiac cycle is a sign of

diminished orthostatic stability of cosmonauts during the flight. It should

be stressed that there was no progressive deterioration of orthostatic

stability with increase in duration of the flight.

The reaction to LBNP depends significantly on volume of circulating blood

(CBV)[6, 7]. No direct studies of CBV were made during the flight. But,

36
according to circulatory indices during LBNP, no appreciable differences could

be noted between the 14th, 21st and 31st days. Hence, it may be assumed that

all of the CBV changes are stabilized sooner, i.e., not later than the 2d

week of weightlessness. Nor could we demonstrate a clearcut correlation

between filling of jugular veins and blood pressure in them, on the one hand,

and reactions to LBNP, on the other. Thus, for the 1st month of the mission,

the blood pressure in the jugular veins of V. I. Sevast'yanov was higher than

the initial level, and in the 2d month it became the same as the latter, or

even lower. Probably, with LBNP in weightlessness, the body retains the

capacity to rapidly mobilize deposited blood. As a result, endurance of

the test with lowering of central venous pressure remains at a similar level.

Apparently, an analogous process takes place during physical training and work.

The choice of LBNP for functional tests is a timely practical question, since

it is related to safety of tests during missions.

On the Skylab station and in the preflight and postflight examinations of

astronauts on the Apollo program, American researchers [2] used a test

with gradual [in steps] lowering of pressure to -50 mm Hg with total duration of 15 min.

There were cases of a presyncopic state among crew members of the first expedition on the Skylab station when the test was performed during the flight, and

this served as the reason for limiting pressure drop to -40 mm Hg for a

total of 10 min. The system used to lower pressure with LBNP on Salyut

orbital stations has not changed since 1974 [1]. It was tested repeatedly

in preflight and postflight examinations of the crews of Soyuz-12 and Soyuz~16.

There were no instances of worsening of the condition of the cosmonauts. The

advantage of less marked pressure lowering is that there is moderate influx

of blood to thoracic organs with equalization of pressure in the space.

This eliminates, to a significant extent, the danger of appearance of

cardiac dysrhythmia and other adverse reactions. After the two expeditions

on the Salyut-4 station, there was broadening of opportunity for comparative

analysis of Informativeness of a wide set of hemodynamic indices and choice

of criteria of endurance of the test with LBNP.

Of the recorded circulatory indices, the greatest significance was attributed

to dynamics of heart rate, changes in arterial pressure, cardiac output and

elastic properties of arteries. Orthostatic endurance was close to the

preflight level in P. I. Klimuk on the 37th day and, according to some data

(change in phase structure of the cardiac cycle), on the 31st day. On the

37th day, it apparently also improved in V. I. Sevast'yanov- Consequently,

signs of normalization of the reaction to redistribution of blood in the

lower half of the body were observed toward the end of the 1st or start

of the 2d month of the flight.

In the LBNP test 6 h after landing, the changes in output were on the level

of maximum values recorded in flight. According to the results of the investigation, it can be concluded that, in weightlessness, with LBNP of 25-35 mm Hg

lasting 5 min, acceleration of heart rate could reach 30-40%, decrease in

37
stroke volume constituted 50-55% and minute volume, 30-37%, with 20-30%

increase in velocity of pulse wave in the aorta.

The significance of reorganization of cardiac cycle phases merits re-evaluation.

On the ground, a 50% or greater increase in interphase coefficient K, with

35 mm Hg LBNP is prognostically unfavorable.

In weightlessness, during LBNP of 35 mm Hg, other conditions being equal

(decreased stroke and minute volumes, faster pulse, etc.), there are more

significant changes in phases of isovolumetric contraction and expulsion.

The interphase coefficient could increase by 70%. After landing, everything

appears to revert to its place.

There was an appreciable difference in dynamics of recovery of weight and

balance of intake and output of fluid between the commander and flight engineer.

These indices were better in P. I. Klimuk, and on the 4th-6th day his orthostatic stability was similar to the preflight level. The fluid balance became

negative at the end of the 3d day and weight loss constituted 800 g in V. I.

Sevast'yanov. By the 6th day, his orthostatic stability worsened again.

Thus, 63-day weightlessness elicits reorganization of extracardiac and intracardiac hemodynamics and worsens the circulatory reaction to LBNP, which

should be interpreted as a manifestation of deconditioning of the cardiovascular system and diminished orthostatic stability in the inflight and

postflight periods.

BIBLIOGRAPHY

1. Batenchuk-Tusko, T. V.; Degtyarev, V. A.; Popov, I. I.; et al. in:

"Nevesomost"' [Weightlessness], Moscow, 1974, pp 132-157.

2. Johnson, R. L. in: "Man in Space," Moscow, 1974, pp 142-163.

3. Andriyako, L. Ya. "Change in Function of the Human Cardiovascular System

During the Functional Test With Lower Body Negative Pressure," author

abstract of candidatorial dissertation, Moscow, 1975.

4. Voskresenskiy, A. D.; Kalmykova, N. D.; and Kirillova, Z. A. KOSMICHESKAYA

BIOL. [Space Biology], No 1, 1974, pp 23-29.

5. Degtyarev, V. A.; Doroshev, V. G.; Kalmykova, N. D.; et al. Ibid, No 3,

PP 47-53.

6. Gayton, A. "Physiology of Circulation. Minute Volume of the Heart and

Regulation Thereof," Moscow, 1969.

7. Marshall, R. D., and Shepherd, J. "Cardiac Function In the Healthy and

Sick," Moscow, 1972.

38
UDC: 61.2.76-06:613.693

DYNAMICS OF ORTHOSTATIC STABILITY OF COSMONAUTS FOLLOWING 2 TO 63-DAY

MISSIONS

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 31-37

[Article by V. V. Kalinichenko, submitted 25 Mar 76]

[Text] It is known that cosmonauts always experience difficulties in readaptation to earth's gravitation after space flights, chiefly due to deconditioning of the circulatory system [1-4]. For this reason, it is deemed

purposeful to summarize some of the results of studying orthostatic stability

(OS)[or endurance] of 25 crew members of Soyuz-4—Soyuz-18 spacecraft [SC]

including postflight studies after missions on the Salyut-3 and Salyut-4

orbital stations (OR).

Method

OS was determined 6 and 1 month before the flights. Postflight studies were

conducted mainly at the following times: 2-8 h after landing (0 day), after

spending the first night on earth (1st day), on the 3d, 7th days, and at

later times following longer missions.

We used two variants of orthostatic tests: active vertical position for 6 min

and passive position on an orthostatic table, with the head 70° up from the

horizontal for 10 min. As a rule, the active orthostatic tests were performed in the morning, when the subjects awakened, and the passive ones

2-3 h after breakfast. Each min of active standing and in even min of

passive standing, we recorded and then calculated the following indices by

the mechanicardiographic method: heart rate (HR).per min; left ventricular

expulsion time; arterial pressure (AP); end systolic pressure (ep); mean

dynamic pressure (m); diastolic pressure (d) in mm Hg; arm/leg lateral

systolic pressure; pulse wave velocity in vessels of the muscular (Vm) and

elastic (Ve) types and ratio between them; stroke index (SI) as the ratio

of systolic volume according to Bremser and Ranke to body surface, in ml/m'

The integral index of orthostatic stability, IIOS, was calculated from the

mean values of the above indices and dynamics thereof in orthostatic position

[5]. It reflected the degree of adequacy of antigravitation mechanisms and

their capacity to compensate for orthostatic perturbance. The ratings

39

2
according to IIOS in arbitrary units (arb.u.) corresponded to the following

five gradations of OS: 86-100, excellent; 71-85, good; 56-70, satisfactory;

41-55, low and less than 41, poor.

In addition, we determined the cardiac index (CI) as the product of SI and

HR, and specific peripheral resistance as ratio of mean dynamic AP to CI.

Results and Discussion

OS was good and excellent in most cosmonauts before the flight, and satisf

tory 1 month prior to the flight in only 4 subjects.

Table 1. Dynamics of integral index of orthostatic stability

acNumbe r

Duration

P reflight Days after flight

ü

months

1

month 0 1st ' 3d 7th Rank

OR

of mg

SS flight

days AOT >OT AOT 3

01 AOTPOT

1

AOT P01 A01 POT KOI POT

12 2 66 05 78 78 42* 05 44 79 77 8

91 90 93 83 58* — 82 70 90 84 3

Hi (i — 80 85 88 ..._ 67 87 85 92 1 — 91 82 75 — 68 70 75 80 __ 2

13 8 81 79 82 73 — 04 70 79 71 77 5 — — 68 68 — 44 42 — 70 00 04 11

9 18 — 07 81* 64 24* — 04 — 08 50 50 48 13 — 81 79* 65 16* — 57 77 54 24 55 14 14 3 16 88 87 87 92 — — 81 04 8? 07 87 8? 6

72 86 82 90 — —. 09 63 74 82 88 73 7

17 4 30 80 05 65 78 — 47 8 10 67 50 71 64 12

82 89 78 78 — 61 06 06 8'? 69 80 79 4

18 4 03 83 81 75 85 __ — 59 70 85 70 76 74 9

72 74 70 85 70 70 01 77 72 05 10

Note: The first of each set of two lines refers to data on the commanders

and the second, to flight engineers.

AOT) active orthostatic test *) AOT performed in the afternoon

POT) passive orthostatic test

Table L illustrates changes in OS only in cosmonauts for whom dynamic determination thereof was made after the flight; it was found to be diminished to

some extent or other in all cases. As to ranking of absolute OS levels and

extent of decline from the preflight levels, the cosmonauts in whom it was

satisfactory .1 month before the mission were ranked as the last four. If

we arbitrarily classify orthostatic deconditioning into mild, moderate and

marked, expressly these four cosmonauts would be referable to the last

category. Thus, this confirms the prognostic significance of initial OS

level. Furthermore, it is expedient to adjust preventive measures against

deconditioning inflight on an individual basis, with due consideration of

preflight OS.

40
It would be purposeful to consider the degree of orthostatic deconditioning

as function of duration of weightlessness separately in cosmonauts who flew

on the Soyuz SC and Salyut OR, in view of the fact that conditions and

measures for the prevention of deconditioning on Salyut OR were better than

on Soyuz SC [6, 7]. According to Table 1, we see that there is a distinct

tendency toward increase in orthostatic deconditioning with increase in duration of flights on the Soyuz SC. There was appreciably greater deconditioning of A. N. Nikolayev and V. I. Sevast'yanov after an 18-day flight than

after shorter ones.

Orthostatic deconditioning also increased with increase in duration of

mission on the Salyut OR. However, this tendency was less marked than after

flights on Soyuz SC. Cosmonauts were not much more deconditioned after

a 63-day flight on Salyut-4 than after a 16-day flight on Salyut-3. Perhaps

the significant difference in orthostatic deconditioning after a 3-day

flight was due to individual differences in endurance of the deleterious

effect of weightlessness. The sharp decrease of OS in the commander of this

crew on the 1st postflight day is not typical for the group under study in

these conditions.

Intensification of deconditioning and increased stability of altered regulation of the circulatory system with increase in duration of weightlessness

result in slower and incomplete restoration of OS in the first days of readaptation following long flights (Figures 1 and 2). This is also confirmed

by the rate of recovery of circulation volume in orthostasis. On the day

the cosmonauts landed, CI was usually lower than the preflight level, in

spite of higher HR. However, circulatory volume rapidly increased under

the influence of earth's gravitation after flights lasting up to 16 days, and

in 1 day on earth the CI was above the preflight level (Table 2). After a

63-day flight, CI did not reach the preflight level in the same time.

Figure 1.

Change in IIOS in passive orthostatic

tests on cosmonauts following missions

on Soyuz spacecraft.

X-axis: left scale, absolute value of

integral index 1. month before flight;

right scale, change in integral index

after flight, % of absolute preflight

data. The numbers refer to duration of

missions; white circles, data for craft

commanders; black circles, data for

flight engineers

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42
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Figure 2.

Same as Figure 1, but following flights

in Salyut orbital station

0 1 2 3 4 5 6 7 8 9 WJmi3K15!6

Postflight days

Thus, the studies revealed that there is an increase in orthostatic deconditioning with increase in exposure to weightlessness. However, the rate of

increase therein is appreciably lowered by measures to prevent the adverse

effects of weightlessness.

At the present time there is no question about the importance of measures to

prevent deconditioning. Already after the 2-day flight of A. S. Yeliseyev

and Ye. V. Khrunov, which involved passage from one SC to another through

open space, it could be considered that their physical activity during the

flight aided in good preservation of OS. Thus, 1 day after landing, their

OS constituted 105 and 109% of preflight levels. In contrast, the fact

that the crew of Soyuz-12 was less active in another 2-day mission was

apparently one of the reasons why their OS constituted only 71 and 95% of

preflight levels after 1 day back on earth. Evidently, the better system

of preventive measures against the deleterious effect of weightlessness on

Salyut OR was more effective in counteracting orthostatic deconditioning

than during the missions on Soyuz spacecraft. Thus, after a 63-day flight

in Salyut-3, the cosmonauts were less deconditioned than after an 18-day

mission in Soyuz-9. It is significant that the same flight engineer, V. I.

Sevast'ysmov, participated in both flights.

In most cases, there was uniform and rather rapid recovery of OS. In these

cases, we could refer to adequate preservation of functional reserves of the

circulatory system. There was slower recovery of OS in cosmonauts after

the 18-day mission on Soyuz-9 and the 63-day one on Salyut-4. These cosmonauts presented a second decrease of OS at the end of the 1st week of readaptation. This suggests overfatigue of regulatory mechanisms of the circulatory system under the influence of earth's gravitation that is perceived

by the cosmonauts as hypergravitation after being weightless. Evidently, an

excessively active motor regimen played a substantial role following the

18-day mission.

43
The marked and early secondary decline of OS on the 1st day after a 30-day

mission in the commander was probably largely due to inertness of humoral

mechanisms of circulatory homeostasis. This assumption is confirmed by the

good rate of OS recovery on the next days. In this regard, the rapid

OS recovery of cosmonauts after a 30-day mission, as compared to a 63-day

flight, merits attention. Perhaps the pharmacological agents with anabolic

action given to the cosmonauts after the 30-day flight, but not after the

63-day mission, were beneficial.

It is purposeful to supplement the general description of OS changes with

consideration of some special mechanisms of orthostatic reactions. Retention

of the capacity to increase arterial tonus is beneficial, according to

velocity of pulse wave and peripheral resistance, and in the case of a significant decrease in circulatory volume as, for example, in the cosmonauts

after an 18-day flight [8], this mechanism becomes the principal and,

apparently, last reserve for compensation of inadequate venous return. The

tendency toward decreased arterial tonus and peripheral resistance in orthostasis was only observed in the craft commander on the 1st day after a 30-day

flight. For this reason, the still satisfactory circulation volume (CI =

1740 ml/min/m ) was not enough to provide the necessary delivery of blood

to vital organs, and the test was interrupted prematurely (see Table 2). The

fact that CI rises to above preflight levels in cosmonauts after 1 day on

earth following missions lasting up to 30 days could be an indication of

increased venous tonus as well. But the slow increase in vascular tonus

under the influence of earth's gravitation must be considered the main

cause of marked orthostatic instability in the first minutes and hours after

landing. Evidently, the problem is to activate it at the final stage of

the mission.

Considering that deficient venous return is the chief cause of postflight

orthostatic instability, it is interesting to discuss the change in

severity of orthostatic tachycardia, with due consideration of active pumping in of blood by the heart [9]. Perhaps, tachycardia in orthostasis is

not only an index of intensity of antigravitation mechanisms, but an

effective component of the orthostatic reflex. According to data of both

American researchers [10] and our own (see Table 2), in orthostasis the HR

increases with increase in flight duration to 8 days, reflecting a corresponding decrease of OS. With further increase in duration of flights, there

is a tendency toward decrease in orthostatic tachycardia. One could hardly

Interpret this tendency was a beneficial phenomenon. For example, even

with sharp decrease in OS of cosmonauts after an 18-day flight and in the

commander after a 30-day flight, HR constituted 120-124 beats/min and was

inadequate to supply the required volume of circulation. Thus, with increase

in duration of flight, apparently there is an increase in involvement of

the cardiac component in lowering OS.

A comparison of changes in endurance of active and passive standing indicates

that deconditioning of the vascular component plays a larger part in insufficiency of the venous return. At the same time, the functional capabilities

of the muscular pump remain relatively high. Thus, while preflight endurance

44
of both types of orthostatic loads was virtually the same in the subjects

(IIOS 82 arb. u.), endurance of passive standing was poorer than active,

with statistical reliability (P = 0.01) after the flight. On this basis,

we could recommend exercise, in the form of walking, stepping from one foot

to the other, etc., for cosmonauts in order to prevent orthostatic disorders.

Apparently, the postflight change in OS of cosmonauts depends on several

factors. The initial level of OS, duration of flight, living conditions in

the spacecraft and system of prevention of decondition, as well as readaptation regimen appear to be the most important ones. Other factors, that are

difficult to take into consideration, are also significant.

The limited number of observations means that our results are merely preliminary. At the same time, the methods developed to study orthostatic stability may be useful in determining the chief causes of decrease thereof.

BIBLIOGRAPHY

1. Gurovskiy, N. N.; Yegorov, A. D.; Kakurin, L. I.; et al. in:

"Nevesomost"' [Weightlessness], Moscow, 1974, pp 116-132.

2. Kakurin, L. I.; Gornago, V. A.; Katkovskiy, B. S.; et al. in:

"Kosmicheskaya biologiya i aviakosmicheskaya meditsina. Tezisy

dokladov na 4-y Vsesoyuzn. konferentsii" [Space Biology and Aerospace

Medicine. Summaries of Papers Delivered at the 4th Ail-Union Conference], Moscow—Kaluga, Vol 1, 1972, pp 71-73.

3. Pestov, I. D., and Geratevol', Z. Dzh. in: "Osnovy kosmicheskoy

biologii i meditsiny" [Fundamentals of Space Biology and Medicine],

Moscow, Vol 2, Book 1, 1975, pp 324-369.

4. Berry, Ch. A. in "Bioastronautics Data Book," NASA Sp-3006,

Washington, 1973, pp 349-415.

5. Kalinichesnko, V. V. in: "Problem aviatsionnoy i kosmicheskoy medistiny"

. [Problems of Aviation and Space Medicine], Moscow, 1975.

6. Gurovskiy, N. N.; Yeremin, A. V.; Gazenko, 0. G.; et al. KOSMICHESKAYA

BIOL. [Space Biology], No 2, 1975, pp 48-54.

7. Stepantsov, V. 1.; Yeremin, A. V.; and Tikhonov, M. A. in: "Nevesomost','

Moscow, 1974, pp 298-314.

8. Kalinichenko, V. V.; Gornago, V. A.; Machinskiy, G. V.; et al.

KOSMICHESKAYA BIOL., No 6, 1970, pp 68-77.

9. Amosov, N. M.; Lishchuk, V. A.; Patskina, S. A.; et al. "Self-Regulation of the Heart," Kiev, 1969.

10. Berry, Ch. A.; Coons, D. 0.; Catterson, A. D.; et al. in: Gemini MidProgram Conference," NASA SP-121, Houston, 1966, pp 235-261.

45

1
UDC: 629.78:612.821]:614.25

SOME PSYCHONEUROLOGICAL REQUIREMENTS IN ASSESSING INFLIGHT FUNCTIONAL

STATE OF COSMONAUTS

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 37-39

[Article by V. I. Myasnikov, 0. V. Kon'kova and F. N. Uskov, submitted

2 Dec 74]

[Text] The neuropsychiatrist who evaluates the current state of cosmonauts

during missions has to work under specific conditions. They include the

brief communication sessions, limited input of information about the cosmonaut's condition, inevitable interference, limited free verbal exchanges

between neuropsychiatrist and cosmonaut, need for operational [immediate]

conclusions and recommendations. As a result, the expert may feel that

there is a shortage of information, i.e., he may be in a vague situation.

This becomes particularly perceptible when he has to establish a similarity

between a current state and its initial "level," that is typical for the

individual under observation.

Our objective was to demonstrate the distinctive features of assessment of

similarity on the basis of incomplete information.

Methods

In selecting methods for our study, we tried to obtain an experimental situation that would reflect, as fully as possible, the dynamic aspect of the

process of judging similarity. For this purpose, we referred to synonym

dictionaries and consulted linguists to select two series of synonyms, with

different mechanisms involved in evaluation of similarity of meaning. The

first series of synonyms was: examine, view [inspect], scrutinize, look

closely and pore over; similarity of synonyms as to meaning could be

determined both on the basis of direct estimation of similarity and use of

the discursive approach. The second series of synonyms—negative, denying,

disapproving, unflattering, unfavorable— was less suitable for discursive

approach to similarity of meaning than the first one; here, determination

of similarity was based on the direct impression. This was indicated by

the results of a special experiment we conducted with the participation of

20 people with various (secondary, specialized and higher) levels of education.

46
After being shown a series of synonyms, they were asked to describe verbally

the similarity and difference in meanings of the synonyms in the series. It

was found that, regardless of knowledge of language, this problem presented

great difficulties for the "negative" series of synonyms, and in some cases

could not be done at all. At the same time, the similarity and difference

between synonyms in the second series ("examine") could be better described

verbally.

The second methodological procedure which, in our opinion, reflects the

dynamics of the thinking activity in the process of judging similarity of

synonyms, was to use a procedure of one of the psychometric methods, the

triad method [1], which made it possible to provide a quantitative expression

of the opinions of the subjects about similarity of compared stimuli on

the basis of multiple comparison of stimuli in all sorts of combinations.

In this investigation, what was important from the standpoint of dynamics of

judgments was also the fact that the experiment was conducted as well in

an altered functional state. For this purpose, the subjects took psychopharmacological agents referable to different groups.

Experimental procedure: In accordance with the triad method we used, the

synonyms were put in all possible combinations of three, i.e., triads.

After keying the synonyms of any series with the letters a, b, c, d, e,

we obtain the following combinations: a b c, b

d

e, d a e, etc. Each triad

is presented three times, and the reciprocal position of the stimuli (synonyms)

has to be changed. For example, for the triad a b c We obtain two more:

c

a

b and b

c

a. Thus, we have 30 triads in all. The immediate task for

the subject was formulated in the instructions as follows: "You will be

shown cards, such as:

keen

precise correct

Your task is to read the top word. Explain its meaning. Then read the other

two words and decide which is closest in meaning to the top one. If this

applies to the word on the left (precise), place the card to the left, and

if it applies to the word on the right (correct), place the card to the right.

In order to increase diversity in the subject's performance, the triads referable to both series were presented in the same test, being shuffled with one

another and 36 "ballast triads" in random order. Thus, there was a total of

96 triads; the entire set was presented in two sessions with a 30-min break

between them.

Drug experiment: Under controlled conditions (use of placebo) we tested

ptridrol (4 mg), tisercin (25 mg), and aminazine (25 mg). The drugs were

ingested in starch capsules. To assure a more rigid placebo control, the

instructions pertaining to the drugs were vague. The subjects began to work

with the triads 1 h after intake of the capsule. The procedure for presenting

synonyms in the drug series did not differ from the background. In all, we

conducted five series of experiments: I) background, II) placebo experiment,

III) tisercin, IV) piridrol and V) aminazine.

47
SaduaJed'frofrvnf *T* 1° ^** of 8 men ^~^ Years of age who had graduated from a VUZ and worked in the same field.

The results were processed separately for each series of synonyms. In our

experiments the opinions as to similarity of meaning of synonyms were reflected xn the results of the choices the subjects made for each triad. On

thxs basis we calculated the index of stability of judgment, i.e., number

tf thrLcJrnH

S

^

JeC\Chan8ed hlS mind ln the dru§seri^> as --Pared to the background (for the entire set of triads),-ZQ [Pm probably refers

in differLrfSf°

r

^T ^ ^' ^ -liabili^fofdJfSnSs in"J in different serxes was determined by using the theorem of Moivre-Laplace

with a preset significance level of P - 0.05. We processed triads for

which at least one subject gave the same opinion in all series.

Results and Discussion

A comparison of ZQ in the placebo series to the ZQnm in the drug series

TTIIIU n° Tl±St

iC

^

ly Si*nificant differences inP

compared values "he

llnl WH ,,

th

*.fluctuations of ZQ from series to series were negliconcludid rW T • *? "^ 8er5es °

f a

^onyms. Hence, it could be concluded that changes in functional state do not affect the process of

SatnfhiUrS-nt:8f

a

%

t

Ki8jnili

arlty °f Syn°nym meanin8s

' since our data show "

remain^ cZT r ^ ^

UnStable °einions

» as compared to the background, remains constant in all series.

feries TtJ^T' "*" ^f^ ^

the h±& values of ZQpm in the second

sLnificant^n YrVaST^ ^ ^

fir8t; th±S dif^ ^enc^'was statistically sxgnxlicant xn the tests with tisercin.

The obtained facts indicate that, although the opinionsas to similarity of

meaning in both series of system are stable, as related to the initial!

serie8s and tMi'," aCtUa\

leV£*of this stability is lower in the "negative"

Thus" It- 1. I is apparently related to the nature of judgments made here.

in tir LT < c opinions made on the basis of immediate impressions,

xn situations wnere information is incomplete, are more subject to instability

festeaUSrtS° V

1

"""

1 natu"" ^ our experiments,'this was mani- "

fested because of altered functional state of the subjects.

ltrtTTrated fr

tS

r

8t

^

taken int°consideration in a real situation

1H gn?

S mad!- ^V±eW °f the faCt that>in th* case of opera- tional diagnostics according to incomplete data there is a definitely high

Pinion, °

Plni0nS ab°Ut Parity according to immediate impressions, such

° f

are S

^

JeC

,

C t0

u

hangeS ±n functional state, and this must be

Laken into consideration when deciding on the optimum work schedule for

an expert xn shifts. Individual characteristics of stability of such judgments may also be quite important in the work of an expert neuropsychiatrfst.

of soT\ L t ^ ^-the Tabl6'

the degree °f

-stability of opinions of some subjects according to the immediate impressions about similarity of

synonyms may be particularly high (subjects 6 and 7). In all probability,

fnlluTilTZTnT\1S°T ?' tb1

C3USeS °f dlminish^ accuracy of these opinions, including verbal formulation of a conclusion by an expert. For this reason.

48
determination of dissimilarities in synonym meaning could be used as a

unique functional test for the expert.

Number of times subjects changed their minds about similarity of synonyms,

as compared to background

1st syn.: examine, view, scrutinize, look closelv, pore over

Subjects

Series

i

o rs 4Tj 4) 8

B

fX

P

1

II

III

IV

V

o

7

5

2

12

4

3

7

2

4

7

0

5

6

5

7

5

3

1

6

4

5

0

3

4

3

5

1

5

3

5

3

39

29

31

35

2Qpm for all serie s 10 26 19 23 15 12 13 16 134

2d syn.: negative, denying,disapproving, unflattering, unfavorable

Series

Sub-jects

l -

.1 4 .*) li 1 7

1

8 1o11

III

IV

V

3

0

5

0

10

4

3

3

5

5

7

4

7

3

9

10

5

2

7

5

('.

7

8

8

11

10

4

7

7

8

4

3

54

45*

47

40

^pin for a 1 1 serk'ji 20

1

20 21 29 19 29* 32* 22 192*

*With P = 0.05 it can be maintained that ZQ of the 2d series of synonyms

are greater than those of the 1st series.

On the whole, this study enables us to consider that investigation of the

psychological structure of expert activity is a rather productive approach

to defining criteria for screening and purposeful training thereof.

BIBLIOGRAPHY

1. Guilford, J. P. in: "Psychometric Methods," New York, 1954, p 192.

49
UDC: 612.3-06:613.693

HISTOCHEMICAL STUDY OF DIGESTIVE ORGANS OF RATS FOLLOWING FLIGHT ON KOSMOS-605

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian No 3,

1977 pp 40-46

[Article by M. G. Shubich, L. L. Goryacheva, V. I. Dudetskiy, N. M. Lutsenko

and G. M. Mogil'naya, submitted 25 May 76]

[Text] A comparative study was made of the stomach, small and large intestine,

and pancreas of rats that had spent 22.5 days onboard Kosmos-605 satellite,

as well as rats from a ground-based model experiment and intact rats maintained

on the same diet in a vivarium.

Methods

Material was taken for this study after completion of the flight and groundbased experiments: 8 rats were examined on the 2d postflight day and 5 after

the ground-based experiment. There were as many control rats as experimental

ones.

Tissue specimens were fixed in Gamperl, Carnoy and Becker mixtures, then imbedded

in paraffin. Organ preparations stained with hematoxylin-eosin, picrofuchsin

according to van Gieson and methanyl yellow with additional staining of nuclei

according to Feulgen were submitted to histological examination. Polysaccharides and glycoproteins, demonstrated by means of a set of histochemical

methods, including the PAS method of A. L. Shabadash [1], basic brown stain

at pH 1.0 according to M. G. Shubich [2] and alcian blue at a pH of 2.7 according to Mowry [3]. The demonstrated carbohydrates were identified by the

system of M. G. Shubich et al. [4]. The set of histochemical methods described by M. G. Shubich et al. [5] was used for demonstration of proteins of

pancreatic acinar cells.

A combined ocular grid was used to calculate volumetric proportions of the

substances studied according to G. G. Avtandilov [6]. According to the data

of this author, the percentage of points coinciding with stained microstructures characterizes the share occupied by the substance in question both

in the overall area and overall volume of examined preparations. Lymphoid

cells were counted per 0.16 mm square of an ocular grid.

50
Results and Discussion

The mucosa of the stomach and intestine of experimental rats did not differ

essentially from that of control animals with regard to histological structure. Epithelial cover cells were missing from some parts of the mucosa

in only a few of the rats in the flight group and model experiment on the

2d day after the tests. Dilatation of blood vessles in the wall of the

stomach and intestine was observed in experimental and control rats.

Along with minor edema of the stroma of some villi in their apical region,

there was lamination and fragmentation of epithelium of the duodenum of some

animals in the model experiment, on the 2d and 27th days after termination

thereof. Analogous changes were observed in the jejunum of some control

animals and rats in the flight group. It is difficult to relate these

changes to the effects of experimental factors since, according to the data

of M. A. Vorontsova and L. D. Liozner [7], desquamation of epithelia cells

at the apex of intestinal villi of rats and dogs is a normal phenomenon, and

it is an expression of the process of physiological regeneration of the

epithelium. Vascular dilatation could be the result of sacrificing the

animals.

We examined the condition of the lymphoid system of the stomach and intestine

by counting lymphoid cells on the surface and deep in the lamina propria of

the mucosa. Estimates revealed that the number of lymphoid elements diminished only deep in the gastric mucosa, by 34% as compared to the control

(P<0.05) on the 2d day after the model experiment. As compared to the control, the number of lymphoid elements in the duodenum and jejunum, in

the stroma of the villi, increased by 88% (P<0.02) and 110% (P<0.001), respectively, and by 140% (P<0.005) and 30% (P<0.02), as compared to the number

of such elements in the flight group of rats. On the 2d postflight day, the

number of lymphoid elements in the jejunum increased by 61%, as compared to

the control (P<0.01). There was a 66% increase in amount of lymphoid elements in the colon of animals in the ground-based experiment, as compared to

the control (P<0.05).

It is difficult to derive definite conclusions from these data. Perhaps, the

observed changes reflect phasic changes in migration of lymphoid cells to

areolar connective tissue of the gastrointestinal tract from small blood

vessels. We did not visually demonstrate changes in number and morphology

of follicles of the walls of the stomach and intestine of intact animals and

experimental groups of rats.

In control animals, staining by the PAS method revealed intensive staining

of extracellular secretions and apical regions of the cytoplasm of cover

cells of the gastric epithelium (Figure la). Extracellular secretions presented the most intensive reaction to basic brown. In the lower two-thirds

of the gastric cryptae, secretions stained with this dye were demonstrable in

the apical part of all epithelial cells. With alcian blue, the extracellular

secretion demonstrated an intensive reaction, while the epithelium of the

upper third of the gastric cryptae and some cells of the surface epithelium

51
reacted faintly. A moderate reaction was demonstrated in the epithelium of

the lower two-thirds of the gastric fossae (Figure lb). This warrants the

belief that extracellular secretions and secretions of the gastric cover

epithelium contain a neutral carbohydrate component, sulfosaccharides and

sialosaccharides. Sulfosaccharides were demonstrable in small quantities in

the surface epithelium, and sialosaccharides, only in isolated cells.

In fundal cells of the stomach, carbohydrates were present only in the mucocytes of the necks and secretory segment. Both variants of mycocytes were

distinctly stained by the PAS method (see Figure 1). The neck mucocytes

were also stained with basic brown and alcian blue. A few mucocytes reacted

to basic brown and alcian blue in the secretory segment of fundal glands.

The obtained data indicate that there are a neutral carbohydrate component,

sulfosaccharides and sialosaccharides in mucocytes of the necks and a few

mucocytes of the secretory segment. Most mucocytes of the secretory segment

of the glands contain only a neutral carbohydrate component. According to

morphometric studies, PAS-positive carbohydrates constitute a mean of 66.5%

in the epithelium of gastric cryptae.

On the 2d postflight day, the neutral carbohydrate component had disappeared

from the cytoplasm of mucocytes in the secretory segment of fundal glands.

There was also a sharp decrease of this component in the cytoplasm of

cryptal epithelial cells. Some decrease in neutral carbohydrate component

was also inherent in the cytoplasm of mucocytes of the necks of fundal

glands. Some cells appeared in the surface epithelium, which failed to

demonstrate neutral carbohydrates, and the overall amount of these substances

diminished (Figure 2a). There was a sharp decrease in sialosaccharide content

of extracellular secretions, cytoplasm of cryptal epithelial cells, as well as

mucocytes of the neck and secretory segment (Figure 2b). Decreased alcianophilia was associated with a decrease in sulfosaccharide content of surface

epithelium of the upper third of the gastric cryptae. According to morphometric studies, PAS-positive substances in the epithelium of the gastric

cryptae constituted a mean of 48% on the 2d postflight day, i.e., there were

considerably fewer than in the control.

These data are very interesting, since the decreased mucine-producing capacity

of gastric epithelial cells inevitably leads to a decline of protective

properties of the mucous defense barrier with regard to aggressive components

of gastric juice (pepsin, hydrochloric acid). Menguy and Masters [8], Spicer

and Sun [9] attribute importance to these factors in development of acute

ulcerations of the gastrointestinal tract which, according to Selye [10],

is related to a Stressor reaction. Lambert et al. [11] believe, on the basis

of hlstoradioautographic studies, that depressed synthesis of sulfated glycoporteins in gastric epithelium is the cause of peptic ulcers in rats with

immobilization stress. Since it is quite possible that the flight group of

rats could develop a Stressor reaction, one should consider that the histochemical changes in the epithelial lining of the stomach and other mucineproducing cells are related to stress. The observed histochemical changes

are transient, since the carbohydrate content of the microstructures of the

gastric mucosa that we studied corresponded on the whole to the control on

the 27th postflight day. However, the neutral carbohydrate component was still

low in the cell cytoplasm of the lower two-thirds of the cryptal epithelium.

52
t •' ; War JJ L

w

. W '•

<7

' : i

wMSk

;i£fflfk

Figure 1. Stomach of rat in control group. Objective 20x; ocular 7>

Explanation given in the text,

a) PAS staining b) alcian blue, pH 2.7

am

in rr\n;..v

,„.....„.. , ...__».. - fa . » . M

1. ''"VT ;~<

. • > * . •' • . * • • •. I •

!

a

Figure 2.

a) PAS stain

Stomach of rat after flight onboard Kosmos-605 satellite.

Objective 20*; ocular 7*. Explanation given in the text,

b) alcian blue, pH 2.7

53
Both examinations following the model experiment failed to demonstrate

appreciable changes, as compared to the control, in carbohydrate content of

epithelial lining of the stomach and secretory cells.

Small intestine and colon: Histochemical study of carbohydrates revealed

that there is an increase in sialosaccharide and sulfosaccharide content of

goblet cells of the colon on the 2d postflight day. This change, which is

more marked in the upper part of the cryptae, could be related to slower

extrusion of secretions, due to possible impairment of peristaltic function

of the colon. There was either no change or some decrease in the neutral

carbohydrate component of goblet cells of the rat colon.

Pancreas: In control animals, after fixing according to Carnoy, acinar cells

stained with bromphenol blue, pH 8.2, showed uniform staining of the basal

cytoplasm. There is rather intensive staining of nuclear structures: clumps

of chromatin, nucleolus and nuclear membrane. Granules of zymogen, some of

which appear much lighter, are demonstrable in the apical part. "Protsion"

red 2BS, which reacts at pH 5.6 with lysine and histidine residues [11],

stains the zymogen granules, structures of the nucleus and basal cytoplasm

similarly. With deamination, there is a sharp decrease in intensity of the

reaction with "protsion" red. In most of the terminal regions, there is

uniform staining of acinal cells with bromphenol blue and "protsion" red.

In view of the information concerning localization of numerous ribosomes

in the basal part of the cytoplasm of acinar cells [12], as well as the

fact that cation proteins bound with nucleic acids are demonstrable after

fixing according to Carnoy, without elimination of the latter [13], it can

be considered that bromphenol blue stains the cation protein of ribosomes in

the basal part of acinar cells. Staining with this dye of histones of

nuclear chromatin and cation protein of the nucleus which, as we know, is

the center for ribosome synthesis, is an indirect indication of such a

possibility. Apparently bromphenol blue staining of zymogen granules is

related to localization in them of enzymatic proteins of trypsin and

chymotrypsin,that are basic in nature, with IET [isoelectric point] at

pH over 9.0 [14].

On the 2d postflight day, there was loss of uniformity of staining of cation

proteins of acinear cells in different terminal regions. Many of the latter

showed a decrease in cation protein content. The differences that appeared

are probably due to asynchronous synthesis of enzymatic proteins in different acini. On the 27th postflight day, staining of cation protein of acinar

cells was more uniform, while overall intensity of the reaction was higher

than on the 2d postflight day, being close to the control level. These

changes can be related to restoration of biosynthetic activity of acinar

cells.

BIBLIOGRAPHY

1. Shabadash, A. L. IZV. AN SSSR. SER. BIOL. [News of the USSR Academy of

Sciences. Biology Series], No 6, 1947, pp 745-160.

54
2. Shubich, M. G. BYULL. EKSPER. BIOL. [Bulletin of Experimental Biology],

No 2, 1961, pp 116-120.

3. Mowry, R. J. HISTOCHEM. CYTOCHEM., Vol 4, 1956, p 407.

4. Shubich, M. G.; Lopunova, Zh. K.; and Mogil'naya, G. M. ARKH. ANAT.

[Archives of Anatomy], No 1, 1966, pp 71-74.

5. Shubich, M. G.; Rukavtsov, B. I.; Mogil'naya, G. M.; et al. Ibid,

No 4, 1975, p 52.

6. Avtandilov, G. G. ARKH. PAT. [Archives of Pathology], No 6, 1972, p 76.

7. Vorontsova, M. A., and Liozner, L. D. ''Physiological Regeneration,"

Moscow, 1955.

8. Menguy, R., and Masters, I. SURGERY, Vol 54, 1963, pp 19-27.

9. Spicer, S., and Sun, D. AM. J. PATH., Vol 56, 1969, pp 129-151.

10. Selye, H. "Essays on the Adaptation Syndrome," Moscow, 1960.

11. Lambert, R.; Andre, C.; and Martin, F. GASTROENTEROLOGY, Vol 56,

1969, pp 200-205.

12. Permyakov, N. K.; Podol'skiy, A. Ye.; and Titova, G. P. "Ültrastructural

Analysis of the Secretory Cycle of the Pancreas," Moscow, 1972.

13. Erenpreys, Ya. G. ARKH. ANAT., No 12, 1965, pp 3-8.

14. Neurath, G., and Baily, K. (editors) "Proteins," Moscow, Part 2, 1959.

55
UDC: 612.396.11+612.398.11:

547.962.9]-06:612.766.2

MUCOPOLYSACCHARIDES AND COLLAGEN OF TISSUES IN HYPOKINETIC RATS

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 44-48

[Article by P. P. Potapov, submitted 30 Dec 75]

[Text] Substantial changes have been demonstrated in fluid-electrolyte

metabolism of cosmonauts in weightlessness and in subjects kept on strict

bed rest [1, 2]. These disturbances are related primarily to elimination

of the hydrostatic component of blood pressure and redistribution of circulating blood mass [3-5]. Investigation of metabolism of mucopolysaccharides involved in binding and transport of fluid and inorganic ions in

tissues could demonstrate a number of new factors involved in impairing

fluid and electrolyte metabolism in the presence of hypokinesia. It has

also been established that acid glucosaminoglycans may have a substantial

effect on the properties of collagen structures [5]. There is rather

sparse and scattered information about the condition of connective tissue

in the presence of hypokinesia [6-8], and it deals primarily with connective

tissue elements of skeletal muscles. We found no data in the available

literature about the influence of limited mobility on mucopolysaccharide

metabolism.

Our objective was to study the collagen and mucopolysaccharide content of

animal tissues at different stages of hypokinesia and in the recovery period.

Methods

The study was conducted on 98 white rats (40 of which served as a control)

weighing 180-220 g. The control group was kept in the usual vivarium cages.

Experimental animals were put in individual small cages made of plexiglas

to restrict mobility. All of the animals were kept in the same room and

fed a complete diet with water ad lib. The rats were decapitated on the 15th,

30th, 60th and 90th experimental days and on the 15th, 30th and 60th days

of the recovery period following 90-day hypokinesia. Control animals were

sacrificed and examined concurrently with experimental ones. In view of the

fact that different batches of rats were used in the "hypodynamia" and '

"recovery period" series, there was a separate control for each series.

56
Blood serum, tissues of the liver, heart, kidneys, brain and skeletal

muscles from the posterior group of the thigh served as the material to be

studied. Wet tissue was ground in a mortar and treated successively with

acetone and an ether-acetone mixture (3:1) for 1 hour at 37°, according to

the recommendations of Mier and Wood [9]. We assayed hydroxyproline by the

method of Neuman and Logan [10], hexuronic acids by the method of Dische [11]

and hexosamines according to Elson and Morgan [12], in the modification of

Gatt and Berman [13], in dry acetone power hydrolysates of tissues. We

used the same method to assay blood serum hexosamines.

Results and Discussion

Hydroxyproline, hexosamine and hexuronic acid levels in tissues of control

animals remained constant throughout the experiment, so that we were able to

combine control data covering 15-90 days.

Restricted mobility led to a significant increase (39.6%) in hydroxyproline

content of skeletal muscle tissue as early as the 15th experimental day, and

by the 90th day the increment constituted 48.3% (Table 1). On the 15th day

of the recovery period there was some decline of muscle hydroxyproline, but

the level thereof was 8.7% higher than in the control (P<0.01), and it

remained almost constant thereafter to the end of the experiment.

Table 1. Hydroxyprolline content of rat tissues (mg/100 g dry defatted tissue)

during hypokinesia and in the recovery period

HvDok inesia Recovery period

con- 15 30 60 90 con- 15 30 60

Organ Index trol days days days days trol days days days

Skeletal muscle M 226,1

5,0

315,7

8,5

309,0

9,7

334,8

8,7

335,4

7,7

324,4

1,7

352,6

9,5

351,0

11,8

350,2

13,8

25 9 8 8 8 15 8 8 9

p •CO. 01 -C'0.01 -'0,01 -0.01 < 0,01 r-O.Oö >0,05

M 192,4 192,5 195.0 195,0 191,5 195,5 184,8 180,0 201,8

+III 2,0 2,3 2,8 2,4 3,1 2,5 5.4 4,0 4,1

20 9 8 8 8 15 8 8 9

p •>0,9 >0.3 >0.3 >0,8 ->0,05 •CO,01 >0,2

Heart M 300,(i 359.5 300,7 376,0 388,0 343,5 344,0 354,0 341,5

+m 3.2 5,1 5,9 6,4 0,1 4,0 6,7 0,7 5,0

n 20 9 8 8 8 15 8 8 9

p >0,8 >0.9 -•0,05 • -'0,01 , 0,9 >0,10 >0.7

K idnovN M 534,7 533,3 538.4 590,4 582,8 492,2 404,4 483,6 489,5

-\-m 4.9 13,1 4,5 15,5 12,0 4,5 6,5 7,9 7,9

i\ 20 9 8 8 K 15 8 8 9

1' '••0,9 •0.5 • 0,01 -•. 6,01 0,0! •0,3 0,7

Collagen content, assayed according to hydroxyproline, increased reliably

on the 60th and 90th days of hypokinesia, in the heart (by 4.2 and 7.6%,

respectively) and in the kidney (10.4 and 9.0%). Hydroxyproline level of

57
the liver did not differ from the control at all stages of hypokinesia. The

change to normal motor activity led to some decline of hydroxyproline levels

in the liver and kidneys.

Hexosamine content (Table 2) was low in skeletal muscle on the 15th, 30th and

90th days, in the heart on the 30th day, and in the brain on the 60th day of

the experiment. A decline in the liver was demonstrated at all stages of

hypokinesia, and it was the most marked (23.0%) after 30 days. On the 60th

day of restricted mobility, there was an increase in hexosamines of the

heart and skeletal muscle (by 12.6 and 8.9%, respectively), and the tendency

toward increase persisted up to the 90th experimental day in the heart. There

was little change in hexosamine content of the kidney during hypokinesia.

Table 2. Hexosamine and hexuronic acid content of tissues (mg/100 g dry defatted tissue) during hypokinesia and in the recovery period

Hvpokinpsja Recovery period

con- 15 30 60 90 con- 15 30 60

Organ Index trol days days

213,8

4,7

days

257.0

9,0

days trol days days days

Skeletal muse,

muscle .VI

+/7!

230,0

5,4

215.7

5,3

189,8

10.4

249,0 207,0

4,0 7.5

2! 1,5

3,5

285,8

7,5

n 25 9 8 8 8 15 8 8 9

Liv,ir P •r'0,01 ro,oi <0,05 <'0.01 <0,01 <-"0,01 <0,0I

M 492,0 402,0 379,5 411,8 422,3 518,5 552,0 543,0 523,3

"iiTti 9,8 10,0 10,3 11,2 11,4 9.4 11,2 10,ti 9,4

n 21 9 8 8 8 15 8 8 9

Heart P <0,01 •CO, 01 <0,01 <0,01 <T0,05 >0,1 >0,7 Hexos- M 384.2 380.8 349,7 432,9 407,5 469,9 381,6 448,2 448,9

amines rfcm 10,4 8,4 9,1 17,4 16,1 10,2 6,9 10,1 12.1

n 18 9 8 8 8 15 8 8 9

P >0,8 <-0.02 <0,02 >0,2 <-o.oi ~>0,1 "-0,2 Kidney M 1019,4 994,7 1027,5 1032.0 946,5 1202,4 1201,5 1192,5 1161,3

+m 11,4 13.0 17,0 17,0 36,9 19,9 29,7 25.4 24,2

n 20 9 8 8 8 15 8 8 9

, P „ 0,1 -(1,7 '.- 0,5 >0,05 •0,9 .-0.7 • 0,1 Brain M 1450,2 1400,7 1490,3 1387.5 1340,0 1443.3 1449,4 1 158.7 1433,3

-+-m 22,1 29,0 41,8 13,0 30.3 10.4 13,5 33.3, 21,8

n 25 !l 8 8 8 18 8 8 0

!' :~. o. i .-0,4 • 0.01 < 0.01 0,7 .. I) (J 0 7

Skeletal M 03,2 00,7 71 ,0 00.4 08. 1 70,2 120,8 '»2, 1 71,8

musele -f- m 0.7 -H ,8 1,9 1.2 i ,5 2,2 -»-2,7 '•,1 -f 2,2

n 25 <) 8 8 8 iri'~ 8 K 9 A

r •II. 1 :

P

0,01 v.. 0,05 0.01 •..-o.oi 0,01 0.51 neart M 157.0 100.0 149,8 137,3 141,0 170, 1 180.0 159,0 221 .8

+ m 1. 1 7,8 0,3 11,1 10,0 1.0 5,9 8,5 10,1

n 2() <l 8 8 8 15 8 8 0

llexuKidney I' 0,3 0,2 -0,(15 ~ 0.4 -. 0,02 0 1 . 0,01

ronlc M 202,8 220, 1 223,8 239,5 233,8 192,8 207,5 2! 3^3 19i,5

acids +11 4,9 9,9 13,2 9,7 13,3 3,0 7,4 11,8 7,1

n 18 9 8 8 8 15 8 8 9

P . 0,05 -0,05 c 0,01 <-0,05 .0,05 >0.1 -0.8 Brain .1) 300.0 251,0 327.8 259,4 307.5 280,1 332,0 302.5 209.4

±m 5,5 11,2 13,3 7,0 5,1 10,7 12,3 20,5 0.5

n ')') 9 8 8 8 15 8 8 9

P 0,01 "•0,1 I <0.01|>0,0 '0,01 •0.4 j. -0,1

58
The hexosamine level in the rats' blood serum was low, as compared to the

control, on the 30th and 60th experimental days (8.3 and 12,9% decline,

respectively) and rose toward the end of hypokinesia (90th day) by 7.2%

(in all cases, P<0.05).

With the change to normal motor activity, there was rapid normalization of

hexosamine content of kidney and brain tissues. In the recovery period, the

hexosamine level remained quite low in skeletal muscle to the 30th day; however, by the 60th day the levels thereof increased by 14.8%. On the 15th day

of the recovery period, there was a 6.5% rise in hexosamine levels of the

liver and 18.9% drop in the heart; after 60 days of normal motor activity

there was normalization of hexosamine levels in these organs.

We failed to observe a parallel in dynamics of changes in hexosamine and

hexuronic acid content of tissues. This is indicative of impaired balance

of acid and neutral mucopolysaccharides in them.

On the 30th, 60th and 90th experimental days there was a 12.3%, 5.1% and

7.8% elevation, respectively, of hexuronic acid levels (see Table 2) in

skeletal muscle; a rise was observed throughout hypokinesia in the kidneys.

There was a 17.1 and 14.6% decline (P<0.01) of level of acid mucopolysaccharides on the 15th and 60th experimental days, respectively; a tendency toward

decrease was also observed in the heart, particularly at the late stages of

hypokinesia; however, statistical processing revealed that these changes

were unreliable (0.1>P>0.05).

Hexuronic acid levels were high in all tested tissues on the 15th day of the

recovery period. This index reverted to normal in skeletal muscle, kidney

and brain 60 days after returning to normal motor activity. On the 30th day

of the recovery period, there was a tendency toward decline of acid mucopolysaccharide levels in the heart, and significant accumulation thereof was

again observed on the 60th day.

During hypokinesia, there was a decrease in efficiency of tissular respiration

due to separation of oxidation and phosphorylation [4]. This leads to activation of glycolysis [15], which is also indicated by accumulation of lactic

acid in tissues [16]. Under these conditions, phosphoric ethers of hexoses,

which are the immediate precursors of structural components of mucopolysaccharides [17], are used essentialy to meet the energy requirements of the

organism, and less are used for synthesis of hexosamines and hexuronic acids.

The decrease in hexosamines demonstrated in tissues of the liver, skeletal

muscle and heart (at the early stages of hypokinesia) may be attributed to

a relative shortage of phosphoric ethers of hexoses. By the 60th day, there

is some normalization of processes of synthesis of hexosamines in skeletal

muscle and the heart. Under these conditions, the increase in acid mucopolysaccharides of skeletal muscle apparently lags behind the requirements

of connective tissue developing in it. The system of synthesis of acid

mucopolysaccharides is significantly activated, and it does not immediately

readjust to a new level of metabolism in the recovery period. This is the

cause of significant increment of hexuronic acids in muscles on the 15th day

of the recovery period.

59
The return to normal motor activity following prolonged hypokinesia constituted another extreme factor [18, 19] against a pathological background and

depletion of adaptational and regulatory capabilities of the organism. In

the recovery period, the changes in mucopolysaccharide levels of skeletal

muscle, liver, heart and brain were more marked, in a number of cases, than

during hypokinesia, which is indicative of profound disturbances of regulation of mucopolysaccharide synthesis, both during restricted motor activity

and with subsequent change to normal living conditions. The observed

changes, which lead to impairment of optimum correlations in connective

tissue, could alter tissular permeability and cause redistribution of fluid

and electrolytes in the cell-intercellular substance system [2]. Changes in

mucopolysaccharide content of renal tissue could have a particularly substantial effect on fluid and electrolyte metabolism. Pathological changes

in connective tissue structures of skeletal muscles, which develop during

hypokinesia, could have an adverse effect on recovery of muscle function after

returning to the usual motor regimen [4].

The obtained data are indicative of the need for a comprehensive study of

mucopolysaccharide metabolism during hypokinesia, in order to subsequently

consider the desirability of using inhibitors of hyaluronidase, ascorbic

acid and rutin for preventive purposes.

BIBLIOGRAPHY

1. Parin, V. V.; Krupina, T. N.; Mikhaylovskiy, G. P.; et al. KOSMICHESKAYA

BIOL. [Space Biology], No 5, 1970, p 59.

2. Kovalenko, Ye. A., and Krotov, V. P. PAT. FIZIOL. [Pathological Physiology], No 5, 1975, p 64.

3. Fedorov, I. V. NAUCH. DOKL. VYSSH. SHKOLY. BIOL. NAUKI [Scientific

Papers of Higher Institutions of Learning. Biological Sciences], No 12,

1972, p 24.

4. Kovalenko, Ye. A. PAT. FIZIOL., No 3, 1975, p 11.

5. Milch, R. A. in: "Perspectives in Experimental Gerontology," N. W.

Shock (editor), Springfield, 1966, p 109.

6. Bykov, G. P., and Smirnov, V. P. KOSMICHESKAYA BIOL., No 2, 1970, p 46.

7. Mikhaleva, N. P.; Ivanov, I. I.; Fedorov, I. V.; et al. Ibid, No 2, p 42.

8. Portugalov, V. V.; II*ina-Kakuyeva, Ye. I.; and Starostin, V. I. Ibid,

No 3, 1972, p 15.

9. MIer, P. D., and Wood, M. CLIN. CHIM. ACTA, Vol 24, 1969, p 105.

60
10. Neuman, R. E., and Logar, M. A. J. BIOL. CHEM., Vol 184, 1950, p 299.

11. Dische, Z. METH. BIOCHEM. ANAL., Vol 2, 1955, p 313.

12. Elson, L. A., and Morgan, W. T. BIOCHEM. J., Vol 27, 1933, p 1824.

13. Gatt, R., and Berman, E. R. ANALYT. BIOCHEM., Vol 15, 1966, p 167.

14. Kovalenko, Ye. A.; Popkov, V. L.; Kondrat'yev, Yu. I.; et al. PAT.

FIZIOL., No 6, 1970, p 3.

15. Barbashova, Z. I.; Zhukova, Ye. K.; Bablanova, S. M.; et al. in:

"Adaptatsiya k myshechnoy deyatel'nosti i gipokinezii" [Adaptation to

Muscular Activity and Hypokinesia], Novosibirsk, 1970, p 26.

16. Siryk, L. A. BYULL. EKSPER. BIOL. [Bulletin of Experimental Biology],

No 10, 1972, p 22.

17. Rozenfel'd, Ye. L. in: "Khimicheskiye osnovy protessov zhiznedeyatel'nosti

zhiznedeyatel'nosti" [Chemical Bases of Vital Functional Processes],

Moscow, 1962, p 50.

18. Kazaryan, V. A.; Pishchik, V. B.; and Shitov, G. D. in: "Adaptatsiya

k myshechnoy deyatel'nosti i gipokinezii," Novosibirsk, 1970q p 79.

19. Tikhonova, G. P., and Bizin, Yu. P. KOSMICHESKAYA BIOL., No 5, 1974,

P 27.

61
UDC: 612.13-06:612.886

VESlSRUm^CTI0NS T° °

RTH0STATIC TESTS AND HUMAN RESISTANCE TO

Moscow KOSM1CHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, xM11 pp 48-52

[AfAC1

M

h

l

B

;

lm P

°

lyakov'B

-

Ye

- Petrenko, A. B. Sawin, I. G. Tazetdinov and A. M. Tarko, submitted 25 Feb 75]

[Text] It is a known fact that there are wide individual differences between

people wxth regard to degree of predisposition to sea sickness (motion sickness). However, expressly which clinical and physiological distinctions

determxne susceptxbxlxty (or, on the contrary, resistance) of man to motion

sxckness are not yet clear enough.

l

f"f a

f\}

937 l

l}>

the °pinion was voi"d that "weakening of functional

capability of the cardiovascular system and lack of conditioning thereof" is

xnherent xn individuals with a tendency toward sea sickness. This was also

consistent with the findings of M. N. Farfel' [9], who observed that there

is greater increase of heart rate and elevation of arterial pressure during

the orthostatic test in individuals with more marked vegetative vestibular

reactions Castagliulo and Aurucci [10] found a link between the results

of vestibular tests and the test with the tilting table. It consisted of

the fact that 6 out of 10 subjects with vestibular hyperreflexia showed

reactions on the tilted table that bordered on pathological ones. In recent

y

f^' u^S alf°been noted I

2

'

6

> 8] that individuals with low orthostatic stability had a poorer tolerance of vestibular stimuli in a number of

instances.

These data led us to raise the question of using cardiovascular indices to

predict man s resistance to vestibular stimuli.

Methods

Our methodological approach was based on the following considerations: The

organism responds to any stimulus [factor] by altering a number of physiological functions and choosing an optimum mode of vital functions under the

altered conditions. And the nature of transient processes reflects the

distinctions of the corresponding regulatory mechanisms, so that it can serve

as a criterion of their quality [11, 12, 13].

62
We conducted two series of studies. In the first, we studied the correlation

between level of vestibular stability (LVS) and nature of transient processes

in the cardiovascular system during the passive orthostatic test (OTp); in

the second, we studied the analogous correlation to the active orthostatic

test (OTa). The studies were conducted on healthy male volunteers of other

than flying occupations: there were 17 men 18-37 years of age in the 1st

series and 45 in the same age group in the 2d series.

For the OTp, the tilt table with the subject was changed to close to

vertical position (85° angle) for 1-2 s after the subject had stayed in

horizontal position for 10-15 min. We continued the observation for another

10-15 min. We recorded the following continuously: cardiointervalogram (CTG),

rheovasogram of the legs (RVG) and rheoencephalogram (REG). In analyzing

the dynamics of CIG changes, we considered the following parameters: 1) duration of transient process (in min); 2) depth of transient process (in H);

3) fluctuation index (ratio of variance of duration of RR intervals of the

EKG in orthostatic position to the analogous parameter in supine position);

5) variance of RR in supine position (in s); 6) error of mean value of RR

in supine position (in s); 7) mean value of RR in orthostatic position (in s);

8) variance thereof (in s); 9) error thereof (in s); 10) quadratic area of

regulation (in cm, calculated by the method of geometric integration).

In analyzing changes in RVG and REG, we estimated the following: 11) electric

resistance of tissues of the legs in supine position (in ohms); 12) the^same

in orthostatic position; 13) change in parameter 12 in relation to 11 (%);

14) vascular reaction time (in min); 15) RVG wave lag time, in relation to

the Q wave of the EKG in supine position (s); 16) the same in orthostatic

position (s); 17) difference between parameters 15 and 16; 18) change in

amplitude of REG in orthostatic position, as compared to amplitude in supine

position (%); 19, 20) REG wave lag time in supine and erect positions (by

analogy to parameters 15 and 16); 21) difference between parameters 19 and 20.

We usually conducted the OTp test 1 day before the test with motion sickness.

For the OTa, the subject, after lying immobile for 10 min, stood up at the

command of the experimenter in 1-2 s and remained standing for 2 min. The

EKG was taken continuously, starting in the 8th min of supine position to

the end of the test. The following parameters were evaluated in analyzing

the transient process (see Figure): 1) mean duration of ,RR interval in

supine position, Mj (in s); 2) standard deviation of RR interval in supine

position (s); 3) minimum value of RR in erect position (RRmin); 4) difference

between first and third indices (Ax); 5) mean value of RR in erect position

after stabilization of pulse (M2); 6) standard deviation of RR in erect

position; 7) difference between indices 1 and 5 (Ay); 8) maximum value of

RR while standing before stabilization of pulse (A); 9) duration of phase of

acceleration to maximum pulse rate while changing body position (in s, tx);

10) time between maximum acceleration to maximum slowing of pulse while

standing (s, t2); 11) duration of stabilization phase (from time of maximum

slowing to stabilization of rhythm (s, t3); 12) total duration of transient

process, from the moment the subject stood up to stabilization of rhythm (s,

ttot-); 13) difference between standard deviations in supine and erect

63
positions; 14) difference between indices 1 and 8; 15) type of transient process (see below); 16) length of envelope of curve on transient process graph

(cm); 17) area of regulation (cm ).

We distinguished the following types of transient processes: 1) acceleration

of heart rate and gradual, undulant stabilization on a new level (see Figure);

2) acceleration of heart rate followed by a period of overregulation, when

the cardiac intervals are longer during the period of slowing than originally;

3) relatively slow acceleration of rhythm with establishment of a new level

immediately, without slowing phases.

The OTa was conducted 30 min before the test with sea sickness.

The LVS was evaluated according to tolerance of rotating test with accumulation of Coriolis accelerations (ACA) by the method of I. I. Bryanov [3]. The

test was continued until the subjects developed 2d-3d grade vegetative reactions according to the classification used in special ear, nose and throat

expertise, but not over 15 min. The subject's verbal report on his wellbeing (sensation of discomfort, nausea, etc.) during rotation was supplemented

by the results of clinical observation (pallor, hyperhydrosis, overall appearance and behavior) and readings of pulse rate and rhythm, arterial pressure,

skin temperature and external respiration parameters. LVS was expressed in

minutes of endurance of this test. We examined the relationship between

vestibular stability and nature of cardiovascular reactions to the orthostatic

tests by means of correlation and regression analysis.

1st type

2d type

Parameters of transient process

during active orthostatic test

(explained in the text)

3d type

64
Results and Discussion

A study of paired linear correlation between the above parameters, during OTp,

and LVS revealed that none of the coefficients was signifxcant, with confidence coefficient of P = 0.93.

Upon further mathematical analysis, we tested multiple "»^^.^^^

different groups of parameters from the initial set for OTp and LVS in order

to BinSe out groups of parameters that would yield the maximum confidence

coefficient of difference of the corresponding multiple correlation coefficient

<£) from zero. In order to solve this problem, we prepared a special program

that expresses the method of gradient decline in the space of groups of

parameters. Equations of linear multiple regression were devised with

regard to he demonstrated groups of parameters, which expressed the link

between LVS and parameters contained in the group, and we evaluated the

mean-square errors.

The Table lists the coefficients of multiple correlation and regression for

the corresponding parametersin relation to the sought parameter, for

an groujs distinguished, confidence coefficients and estimation of meansquare errors. As can be seen in the Table, there is a substantial correlation between some groups of parameters of the ^^f^^Zt/oefduring the OTp. The sixth group of parameters presented the highest coef

:"J2t of multiple correlation with LVS and the highest confidence coeficien . Thu he optimum model of link between parameters of the reaction

to the passive orthostatic test and LVS (model 6) can be expressed m the

following equation:

Y = -52.8~19.9-X2+32.4-Xlt-3701-X5-421.X6-87.6-X11+195.X12-0.763-X13,

where Y is the sought variable (LVS endurance of test, min); X2, X,, ....

T* are the corresponding 0TP parameters. The mean-square error of the

model equals 2.06 min.

In view of the result obtained, it was deemed purposeful to further search

for Parameters of the initial state that could be measured more readily

Z Jess complex functional tests. For this reason, we conducted a second

series of observations, with OTa and evaluation of the transient process

only according to heart rate. Analysis of the data with estimation of

linear corrections revealed that the corresponding coefficients for parameters "lent process during the OTa and LVS were not statistically

^anifleant (P = 0.9). At the same time, investigation of the optimal

multiple regression enabled us to obtain a model of the following appearance:

Y = 5.14+318.9-Z2-397.7.Z6+0.259.Z1o-0.253.Z12-350.Z13-4.34-Z15+2.71.Z17,

where Y is the sought variable, while Z2, Z6, ..., Z17 are the corresponding

falters of the OTa. The mean-square error of the model equals 4.78 mm

(P = 0.93).

65
Optimum multiple regression coefficients for OTp

o OTp parameter

<i0

0)

I u y

dti c

aicrsSJtn a

R

iH

(1)

O

o i 5 u 11 12 13 15 17 21

/'

1

2

3

14,1

15,9

—2917

—313

—72,0 152 -597 -49,8

—58 —4,22

5,29

— 11,9

3,34

4,07

4,17

0,709

0,451

0.540

0,907

0.772

0,010 4

5

('.

7

21,9

32,4

17,9

-8701

-401

— 421

-288

-87,7 195 -0,703

50,1

70,0

-04,1

5,70

-22,5

-52,8

-7,1

4,23

3,00

2.00

3,51

0,272

0,787

0,935

0,037

0,091

0,978

0,990

0,900

Note: ao is free term of the model.

The obtained data confirmed the existing opinion that there is a relationship

between distinctions of reactions to orthostatic tests characterizing the

initial state of the cardiovascular system and vestibular stability of man.

The mathematical description of this relationship, which we are the first

to submit, in the form of equations of multiple regression opens up the

possibility of making practical use of this fact to predict vestibular

stability depending on the condition of the cardiovascular system.

A comparison of models for active and passive orthostatic tests shows that

the latter included parameters characterizing not only the cardiac, but

vascular component of the orthostatic reaction (parameters 11-13). It

could have been concluded that expressly for this reason the use of this

model permits more accurate prediction of vestibular stability than the

models for OTa. This is also indicated by the insufficient accuracy of

models 2 and 7, in which parameters characterizing only the cardiac component

are represented. This assumption appears plausible, if we consider the

appreciable role of vascular tonus in regulation, both in the case of orthostatic and vestibular stimuli [4, 5].

However, on the other hand, the lower multiple correlation coefficient and

low confidence coefficient for model 3, which contained the same parameters

11-13 (as well as parameter 15) but not a single parameter characterizing the

cardiac component of the orthostatic reaction (as in the case of model 4),

indicates that it is not the vascular component per se that is prognostically

important, but a specific correlation thereof with the cardiac component.

There is also a high degree of coordination of activity of various functional

elements of the cardiovascular system, in which the principle of systems

organization of functions is implemented [1] and thanks to which the

aggregate adaptational effect is obtained. In particular, this is manifested

by maintenance of adequate correlations between changes in minute volume and

peripheral resistance, in spite of the adverse conditions under which the

cardiovascular system functions. Thus, the level of systematism (degree

of coordination of different branches) is apparently the prognostically

most important element, when dealing with the significance of initial state

66
of the cardiovascular system in reactions to vestibular stimuli. Probably,

this is why models 1, 5 and 6, which include parameters referable both to

the cardiac and vascular components, have the highest multiple correlation

coefficients and lower error factor.

The model for OTa did not include parameters characterizing the vascular

component. Perhaps this explains why it is less accurate than the model

for OTp.

BIBLIOGRAPHY

1. Anokhin, P. K. in: "Printsipy sistemnoy organizatsii funktsiy"

[Principles of Systematic Organization of Function], Moscow, 1973,

pp 5-61.

2. Benevolenskaya, T. V.; Boykova, 0. I.; Matsnev, E. I.; et al. in:

"Kosmicheskaya biologiya i aviakosmicheskaya meditsina" [Space Biology

and Aerospace Medicine], Moscow—Kaluga, Vol 2, 1972, pp 23-25.

3. Bryanov, I. I. VOYEN.-MED. ZH. [Military Medical Journal], No 11, 1963,

pp 54-56.

4. Bryanov, I. I.; Degtyarev, V. A.; Lapshin, N. A.; et al. Ibid, No 11,

1966, pp 45-50.

5. Kalashchenko, N. V. in: "Kosmicheskaya biologiya i aviakosmicheskaya

meditsina," Moscow—Kaluga, Vol 2, 1972, pp 188-190.

6. Olovyanishnikov, L. D., and Andronik, K. K. in: "Voprosy

mediko-biologicheskikh issledovaniy" [Problems of Biomedical Research],

Moscow, 1971, pp 40-41.

7. Popov, A. A., and Perchuk, T. M. KAZANSK. MED. ZH. [Kazan' Medical

Journal], No 12, 1937, pp 1407-1419.

8. Usachev, V. V.; Mikhaylovskiy, G. P.; Tatarenova, N. V.; et al. in:

"Kosmicheskaya biologiya i aviakosmicheskaya meditsina," Moscow—Kaluga,

Vol 2, 1972, pp 223-224.

9. Farfel1, M. N. FIZIOL. ZH. SSSR [Physiological Journal of the USSR],

Vol 20, No 2, 1936, pp 286-299.

10. Castagliuobo, P. P., and Aurucci, A. RIV. MED. AERONAUT., Vol 29, No 4,

Suppl, 1966, pp 241-254.

11. "Protsessy regulirovaniya v biologii" [Regulatory Processes in Biology],

edited by P. K. Anokhin, Moscow, 1960.

12. Grodins, F. "Regulation Theory and Biological Systems," Moscow, 1966.

13. (Milsem, Dzh.) "Analysis'of Biological Control Systems," Moscow, 1968,

67
UDC: 629.78.048.4

DYNAMIC CONTROL OF PARAMETERS OF SPACECRAFT ATMOSPHERE

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 53-58

[Article by 1. S. Breslav and V. N. Salazkin, submitted 5 Mar 76]

[Text] With increase in duration of space flights and range of work performed by astronauts, it is growing increasingly important to test the hypotheses expounded long ago concerning the possibility of using a nonstationary

atmosphere in spacecraft (SC) [1, 4, 10]. In this regard, the problem of

implementing dynamic control of atmosphere parameters in such craft ["apparatus"] can be posed.

There are two possible approaches to this problem: 1) "slow" programmed

change and stabilization of atmospheric parameters over considerable periods

of time to prevent the consequences of the deleterious influence of space

factors on the organism; 2) "rapid" control of environment parameters, based

on operational monitoring of body functions, the objective of which is

to provide a high level of cosmonaut efficiency with different load levels

and counteract disturbances of physiological conditions in the case of

abrupt changes in state and conditions of vital functions. In this work,

we shall touch upon some aspects of substantiating expressly this approach.

The main purpose was to determine the patterns of control of partial pressures

of oxygen (P02) and carbon dioxide (PC02) In the SC atmosphere.

Let us first discuss the problem of dynamic, operational control of P02.

In order to define the required patterns of P02 control, we must first provide

mathematical formulation of the general relations between indices of physiological functions to P02 and physical load levels, as the main input effect

[disturbance] on the organism. The results of many experimental studies must

be summarized in order to construct such a model. We used the data referable

to the research in [9], as the first step toward developing the model; in this

study, the authors investigated the established reactions of man to physical

loads varying in force while breathing oxygen and nitrogen mixtures with P02

ranging from 85 to 250 mm Hg. Experiments were conducted on four subjects.

We considered the following parameters: oxygen uptake (V02, liters/min),

oxygenation of arterial blood (S02, %), respiratory minute volume (MV, liters),

68
circulatory minute volume (CMV, liters), rate of cardiac contractions (HR,

beats/min), as well as arteriovenous difference for oxygen (AVO2, ml/liter)

and oxygen utilization coefficient (CUO2, ml/liter).

Identification of the relationships was made using the method of multiple

regression [3]. We found the following functions for the physiological static

parameters of the human body in question as related to oxygen uptake (as the

most adequate index of load level) and ambient PO2:

S02 =27,5—1.02VO.,-f-0,G9PO.2 —0,OOI6PO:, (o - 4,0 R . .0.91). tl)

MV =48,2 U 31,1 VO.,--0,Ü2PO,- 0, 09üVO,PO. [ i,J,'2\0'i - 0,0<>l9POr,

(<!-- ■■ 10,1, R ----0,95), (2)

CMV =21.(i ; 13.5VO.,— 0.2IPO, 0,0I4VO,PO, -- 0,91 \0'i -|- O.MDDI'O-,

(0-— 1,0. R - 0,97), (3)

HR . : 129,1 ~j-03,7VO, -0.97PO.,--5,85VO'^ h 0,0024/JO:j (o - , 7,",, R - 0,97), (4)

AVÜ2 ^ 19,8 -S- 20.4VO., + 0.79PO., + 0.054VO..PO, — 2,83VO| -- 0,0022POH

(a = 6,7, P = 0,94), (5)

CUO = 4,5-}-0,29VO., |- 0.37PO, -|- 0,018VO,PO, — 1,7VOj;~-0,00095PO'i

(a = 4,3, P:=0,78), (0)

where a is standard [mean-square] deviation; R is the coefficient of multiple

correlation. Figure! illustrates the graphs of these functions for a

series of values of VO2 and PO2•

The model equations and graphs indicate that there is linear decrease (by

about 1% per liter V02, [1]) in oxygenation of arterial blood with increase

in load, while the reactions of other parameters of the oxygen transport

system over the tested range of PO2 present extremums that depend on V02.

As we see, the parameter extremums correspond to optimality conditions, i.e.,

conditions of minimum tension of physiological systems: minimal MV, CMV and

HR levels and maximum values for indices of efficiency of oxygen transport,

CUO2 and AVO?. Thus, the model demonstrates that it is possible to optimize

physiological reactions by altering ambient P02. The corresponding patterns

of physiologically optimum P02 control (static) for each parameter can be

determined by using the model of extremum conditions:

'>Fi (VO,, PO,)/dPO., -- 0, (7)

where Fi(V02, P02) is the model equation for a given ith index.

It was found that to optimize the physiological parameters of the organism

the following laws of control of respiratory environment PO2 must apply:

69
Pa;,na,S02 =215, (8)

P0?m\nm =-lG3-;-25,3VO,,, (9)

P0-'minCMV ==- = ' "5

-t- 1 I . 7V0, , (i 0)

/J°-maxAV02: ;

' ~

9

"f- 12,3VO,, (12)

(13)

PO~m,,xCUOr/ = 1 !».'>-! 9,5VO„.

According to equations 8-13, maximum S02 and minimum HR are obtained with

constant (unrelated to load level) values of PO2—215 and 202 mm Hg, respectively. But optimization of other parameters is possible only with

elevation of P02 as the physical load increases. Maximum changes in P02

are required to minimize MV; for this purpose P02 of the atmosphere must

be raised by 25.3 mm Hg for each liter of oxygen uptake per minute.

As we see, the optimality conditions do not coincide for different parameters

of the organism. This shows that a search for the laws of optimum control

of environmental parameters can be made only with the use of an integral

criterion of the state of body functions. Formulation of such a criterion

is a mandatory element in solving the problem under discussion.

Because of the extreme complexity of determination of the required criterion,

this question, of course, exceeds the scope of a single paper. With the

available information, it is deemed the most expedient to use equation 9 for

MV, as an index with maximum sensitivity to PO2 and rather high degree of

integration, as a possible general law in regulating atmospheric P02:

P

°

2

opt

= 163+25.3V02. (14)

Apparently, when using this law of regulation, the required changes in P02

are quite sizable within the possible range of loads.

The dynamic control of oxygen content in the SC^atmosphere can be implemented

in practice by means of systems where not only V02, but other, technically

more suitable indices are used as input physiological information: MV, HR,

VCÜ2, alveolar PCO2 and others. Some relevant laws of control can be

obtained from the submitted model. In particular, when using the parameter

of pulmonary ventilation in the system, as the controlled physiological parameter, the characteristics of optimum P02 regulator have the following

appearance:

PO t = 159+0.81MV-0.0015MV2. (15)

It is feJt that this approach to control of P02 in the respiratory environment can bo used in extravehicular and planetary space suits.

70
ISO

150

120

90

60

——

P02'80,

//20\

'/feg!.

&

//'

2^200

//,

P02^80/

120.V/A

/

/'wer/

/V"^700

120

100

80

SO

40

20

P02;200

j£ (£\

^f20

y

^80

30

25

20

15

10

P02'-8Ö\/s2

/120Y

/

/02OO

/

f

100

90

80

70

60

" ' I —

V02--0,3J£^

//I

—+_._.

i

X _

I

—II--

I

1

—

120

30

60

30

80 120 160 200 240

g

vo2^$*^

\

2

1

V

JL.

v^£

~"-~4Hd -^

SO 120 160 200 240

h

80 !20 160 200 240

45

40

35

30

?t

20

V

I-

°2'%

/\

fj i

i

I

_ 1

7y

SO I20 !SO I'OO 240

j

120 WO 200 240

k

SO 120 160 200 240

1

Figure 1. Effect of P02 of inspired air and V02 of man in a stabilized

state on S02) MV, CMV, HR, AVO and CU02. The vertical

dotted lines refer to value of given physiological parameter with different

V02 and normal P02; solid line connects.extremum points and indicates optimum

P02 and physiological indices for each V02.

I.) V02 (iiter/min) b,h) MV (liters) e,k) AV02 (ml/liter)

II) P02 (mm Hg) c,i) CMV (liters) f,l) CU02 (ml/liter)

a,g) S02 (%) d,j) HR (beats/min)

71
Let us now consider analogously the problem of controlling PC02 in the

SC atmosphere.

When discussing the problems that arise in regulating the composition of

SC atmosphere, one has to take into consideration the possibility of an

unforeseen fall of P02 due to depressurization of the cabin and other causes

that would result in development of hypoxia in the cosmonauts. And, as we

know, hypoxic hypoxia is complicated by hypocapnia due to excessive flushing

of CO2 from blood.

One of the possible means of attenuating the adverse effect of a shortage of

oxygen is to add carbon dioxide to the inspired air; this enhances the

ventilatory reaction to hypoxia and prevents development of hypocapnia.

Indeed, in an experiment where P02 in the chamber fell by almost 50%, addition to the atmosphere of 2-2.5% C02 preserved efficiency of the subjects

for up to 2 days [7]. For this reason, some authors have proposed that the

SC atmosphere be enriched with carbon dioxide to normalize the functional

state of cosmonauts under such emergency situations [5, 6]. However, it has

not yet been determined what specific concentrations of C02 are required to

assure normal exchange of gases in man in the presence of varying levels

of oxygen shortage in the atmosphere.

In order to answer this question, one must establish quantitative functions

between P02, PC02 and indices of respiratory function and oxygen supply

to the organism. An analysis was made of our experiments, which were pursued

to investigate the stabilized reactions of the human body at rest, when

breathing gas mixtures with P02 ranging from 150 to 70 mm Hg, and PC02 from

0 to 40 mm Hg[2]. Thus, a study was made of virtually the entire range of

changes in levels of respiratory gases compatible with human vital functions.

The mathematical description of the required functions was supplied by

the method of multidimensional regression analysis.

Oxygenation of arterial blood is the most informative index of oxygen supply

to the organism. Pulmonary ventilation, as well as HR and CMV are functions

of this parameter to a significant extent. For this reason, in order to

solve the formulated problem, it is first necessary to formulate the

influence of factors that determine the S02 level. Of course, P02 of the

respiratory environment is one of these factors. On the other hand, S02

can be regulated by controlling pulmonary ventilation.

It was found that, in the presence of a hypercapnic stimulus, static MV is

related to PC02 of the atmosphere in the following manner:

MV =8,8-1 0.12PCO, ; 0,0045/V.O-j (a --2.6, R -- 0,79). (IG)

The equation shows that MV can increase by almost 100% within the permissible

r;mge of changes in PC02 .

Taking this possibility into consideration, we obtained S02 as function of

PO2 and PC02 of the respiratory environment:

72
SO, ,--. —51.6-]- 2.08PO, + 0.96PCO,—0,0057PO,PCO,—0,0073/>O*

(a .-=7,1, /? = 0,91). (17>

The last equation makes it possible to determine the effectiveness of adding

CO2 to SC atmosphere when PO2 falls. In particular, one can determine SO2

for different values of atmosphere PC02. It was found, for example, that

SO2 as function of PO2,, in the absence of C02 in the atmosphere and with

maximum permissible concentrations thereof (PC02max = 40 mm Hg in the case

of brief exposure), is defined as follows:

SO, ^ —51, G + 2,08PO, —0,0073PO;;, /"'CO, - , 0

SO, • = --13,2 + \,8bP(), — Q,007:iPOJ, I'CO., -.-. 40

(18)

(19)

Figure 2 illustrates graphs of these functions. The crosshatched segment

of the graph indicates the range of values of S02 when ambient PC02 changes

from 0 to 40 mm Hg.

SOü.%

wo

90

80

70

60

50

L_

Figure 2.

Range of values of oxygenation of human

arterial blood with ambient PO2 from

160 to 60 mm Hg and PC02 from 0 to 40 mm Hg

X-axis, P02 (mm Hg)

80 120 mo

Equation 17 enables us to determine the static characteristics of a regulator

of carbon dioxide level in the SC atmosphere. Such a device could be

executed as a system for regulation of perturbance [input effect], where

the main input effect to be controlled is lowering P02 in the gas environment.

We submit below an equation obtained for such a regulator, the purpose of

which is to maintain oxygenation of blood at the 90% level when atmosphere

P02 falls:

PCih--- !,() (112 •- /'0:!),witti POo<A\2 mm Hg. (20)

73
Pea,, mm Hg

6U \

50

40 \

30

20

10

soz=7oy

L

<soz=

Figure 3.

Partial pressure of carbon dioxide added

to atmosphere with lowering of oxygen

pressure required to stabilized S02 of

man, with S02 = 90% and S02 = 70%.

X-axis, P02 (mm Hg)

8U 1i0

When it is necessary to hold S02 at a level of at least 70%, the characteristics of the PCO2 regulator appear as follows:

PC02=1,8 (83 — POz^with P02<83 mm Hg. (21

Equations 20 and 21 are a linear approximation of the sought functions, or

laws of regulating the body's SO2 under hypoxic conditions by adding CO2

to the atmosphere. Figure 3 illustrates graphs of statistical characteristics of the two PCO2 regulators discussed. By using the patterns obtained

for dynamic control of C02 content of SC atmosphere, it is possible to

optimize oxygen supply for cosmonauts in the case of uncontrollable P02 drop.

The questions discussed in this paper had the objective of determining the

possibility and patterns of dynamic control of parameters of SC atmosphere

as a means of optimizing the functional state of cosmonauts. Unquestionably,

the results obtained require further development. It is too soon to determine the purposefulness of the discussed system of biological control of

parameters of an SC environment. However, it is obvious that "the longer

term prospects related to performance of interplanetary flights advance

such research problems as development of closed ecological systems, minimalization of physiological functions and biological control. The solution

thereof cannot be postponed..." [8].

1.

2.

BIBLIOGRAPHY

Agadzhanyan, N. A. KOSMICH. BIOL. [Space Biology], No 5, 1969, p 3.

Breslav, I. S., Zhironkin, A. G.; Salazkin, V. N.; et al. FIZIOL. ZH.

SSSR [Physiological Journal of the USSR], No 11, 1972, p 1749.

74
3. Breslav, I. S., and Salazkin, V. N. Ibid, No 12, 1974, p 1865.

4. Genin, A. M.; Shepelev, Ye. Ya.; Malkin, V. B., et al. KOSMICHESKAYA

BIOL., No 3, 1969, p 75.

5. Kovalenko, Ye. A., and Chernyakov, I. N. in: "Problemy kosmicheskoy

biologii" [Problems of Space Biology], Moscow, Vol 21, 1972.

6. Malkin, V. B. in: "Osnovy kosmicheskoy biologii i meditsiny"

[Fundamentals of Space Biology and Medicine], Moscow, Vol 2, Book 1,

1975, p 11.

7. Malkin, V. B., and Gazenko, 0. G. DOKL. AN SSSR [Reports of the USSR

Academy of Sciences], Vol 184, 1969, p 995.

8. Parin, V. V., and Gazenko, 0. G. KOSMICHESKAYA BIOL., No 5, 1967, p 5.

9. Hughes, R. L.; Clode, M.; Edwards, R. H.; et al. J. APPL. PHYSIOL.,

Vol 24, 1968, p 336.

10. Lambertsen, C. J. FED. PROC., Vol 22, 1963, p 1046.

75
UDC: 612.21-06:[612.78+612.766.1

MECHANICS OF SPEECH-RELATED RESPIRATION WHILE PERFORMING STATIC PHYSICAL

EXERCISE

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 58-63

[Article by M. A. Tikhonov and A. S. Belan, submitted 21 Jul 75]

[Text] Investigation of the distinctions of speech generation in man

under different living and functioning conditions is of definite interest

to applied physiology, as indicated in particular by the numerous studies

of verbal function in aviation, space and diving practice, in the presence

of diverse emotional and stress states, etc. [1-5].

However, the biomechanical aspects of speech formation, i.e., the correlation between the latter and mechanical and aerodynamic processes in the

lungs and vocal tract, have not bem investigated comprehensively enough

under such conditions.

Our objective here was to make an experimental study of the mechanics of

respiration during speech while performing physical exercises.

Methods

We investigated the distinctions of mechanics of respiration during speech

at rest and with a physical load on 12 essentially healthy males ranging

in age from 18 to 35 years. For this purpose, the subjects in seated position pronounced a standard phrase without muscular tension and while

pulling dynamometer levers toward themselves with a force of 10 kg to

a maximum of 80-100 kg.

We recorded volumetric air flow velocity (pneumotachygram) and the integrated

curve of respiratory volumes (spirogram) during spontaneous respiration and

speech using a mask with built-in Fleisch tube and pneumotachygraph. We

measured transpulmonary intrathoracic pressure in the middle third of the

esophagus in relation to pressure under the mask in five subjects, using a

probe with latex balloon 10 cm long and 1 cm in diameter, filled with 1.5 cm

3

air and a differential electromanometer.

76
Changes in functional residual volume (FRV) of the lungs during physical

exercise were demonstrated using a Krogh spirograph connected to the "bag

in a box" system [6].

Synchronous recording of the pneumotachygram, spirogram and transpulmonary

intrathoracic pressure enabled us to calculate velocity and volume parameters of pulmonary ventilation, respiratory tract resistance [7], as well

to determine subchordal pressure and dynamics thereof during the speech

process. In view of the fact that it is quite difficult to measure subchordal pressure directly, we used a method of indirect determination thereof

by means of correction of transpulmonary intrathoracic pressure measured in

the esophagus [8]. The difference between this pressure and subchordal

pressure corresponds to magnitude of static elastic traction of the lungs [9].

We modified this method to fit the conditions of ordinary speech within the

range of normal respiratory volumes. For this purpose, we first determined

the pressure-volume function for the lungs under quasistatic conditions, i.e.,

with the slowest possible inspiration in relation to level of maximum inspiration to residual volume and plotted a curve of static transpulmonary pressure

as function of change in lung volume (Figure 1, Pst)•

We then recorded

intrathoracic pressure in the esophagus during utterance of a standard

phrase with varying levels of physical exercise (Figure 2) and plotted these

data on the pressure-volume graph. Estimation of volume of phonated* expiration was made as follows: we plotted the volume of prior inspiration on

the y-axis, in relation to level of functional residual volume (determined

from the level of relaxed expiration in the vital capacity test), and from

it we subtracted the expiratory volume during speech, as determined from

the integrated spirogram. The sum of intrathoracic pressure during phonation and pressure of static traction of the lungs produces the flow of air

from the lungs through the constricted rima. This pressure reflects in

essence the level of subchordal pressure (see Figure 1, Pnc) that appears

during speech as a result of constriction of the rima, since the pressure

required to overcome resistance of hypolaryngeal and epiglottic respiratory

tracts during spontaneous respiration constitutes only a negligible part of

intrathoracic pressure.

Results and Discussion

The Table lists the results of quantitative analysis of volume and rate

indices of pulmonary ventilation during ordinary breathing and speech associated with a progressively increasing physical load.

With increase in load, the duration of inspiration prior to phonation diminished, but its volumetric velocity increased, so that the volume of

inspiration increased. Inspiration became deeper, faster and intermittent.

Transpulmonary pressure acquired a higher and higher negative value, thereby

allowing for an increase in velocity of inspiratory flow.

*Hereafter, expiration during speech is referred to as phonated.

77
Dynamics of parameters of respiratory mechanics during speech with different

levels of physical load (M±m)

Inuices of

respiratory

mechanics

Conditions of utterance of phra

without

load

££_

physical load (kg-)

10

Duration of inspiration [Ins] preceding speech \s)

Duration of phonated

Ins (s)

Volume of Ins preceding speech (ml)

Volume of expiration

[Exp] during speech

Difference between

phonated Exp and

prior Ins (ml)

Maximum volumetric

rate of air flow

(liter/s):

in Ins

in Exp

Mean volumetric rate

of air flow during

speech (liter/s)

Maximum intrathoraci

pressure during Ins

(cm water)

Maximum subchordal

pressure during

speech (cm water)

Mean resistance to

expiratory flow

during speech (cm

„water/liter/s)

Respirator tract

resist. (cm w./ 1/s)

during Ins

during unphonated

Exp

1,53±0,02

6,I2±0,06

720±79

940-4-93

214

0,37+0,05

0,19+0,010

0,10+0,01

-4,3±0,25

5,0+1,1

4 1,0+1,(1

2,4+0,17

2,9+0,14

1,46±0,06

5,75±0,07

794+37

1038+74

244

0,43+0,04

0,22+0,012

0,13±0,()5

—8,0+0,34

20,0+1,3

50,0+2,1

2,8-1 0,27

2.8+27

50

1,42±0,03

5,91+0,07

922+53

1177±40

255

0,53+0,05

0,32+0,03

0,17+0,02

7,7+0,50

21,0+1,3

02,0+2,7

2,7+0,24

2,7+0,24

1,21+0,02

5,60+0,05

970+44

1240±51

270

0,06±0,05

0,41+0,02

0,18+0,01

8.7±0,48

28,0+1,8

3,3+0,39

3,3+0,39

80 — 100

50,0+2,3 50,0+3,9

0,91+0,19

4,95±0,04

960+41

1250+38

290

0,98+0,05

0,45+0,2

0,22+0,03

-9,4±0,84

32,2+2,4

3,9+0,20

3,9+0,26

There was also a decrease in duration of expiration during utterance of the

phrase, but it was less marked than that of the prior inspiration, mainly

due to the fact that with large and maximum loads there were pauses in

flow of air prior to the start of expiration, against a background of

maximum elevation of intrathoracic pressure (see Figure 2). There was

negligible change in duration of phonation proper.

78
Figure 1.

Subject L-v. Pressure-volume function for

the lungs and dynamics of hypolaryngeal

pressure during speech.

Y-axis, vital capacity of lungs (liters);

x-axis, transpulmonary intrathoracic

pressure (cm water).

Pst) static transpulmonary pressure

Pnc) subchordal pressure during speech

at rest

P'nc) subchordal pressure during speech

under 50-kg physical load

Figure 2. Subject L-v. Effect of physical load on expiratory dynamics

during speech.

A) speech at rest II) pneumotachygram (liter/s) Ins) inspirali) with 50-kg physical load III) intrathoracic transpulmonary tion

I) Integrated spirogram (liters) pressure (cm water) Exp) expiration

The volume of phonated expiration was consistently greater than the volume

of prior inspiration, and this difference increased with increase in load.

Furthermore, wu observed a decrease in lung volume (with a 50-kg load, FRV

decreased by 480±56 cm ).

With increase in load, subchordal pressure rose significantly, and with a

maximum load it increased by over 100%.

79
There was about the same change in maximum values of expiratory flow rate,

and the rate peaks were often shifted toward the end of the phrase (see

Figures 2 and 3), which could apparently be attributed to dilation of the

rima.

!,c\- Exp

Figure 3.

Subject Sh-y. Changes in volume and

rate indices of pulminary ventilation

during speech

A) at rest

B) maximum load

I) integrated spirogram (liters)

II) pnemotachygram (liter/s)

Figures 1 and 2 show that subchordal pressure of subject L-v fluctuated in

the range of 18-24 cm water during phonation at rest and increased to

26-38 cm water with a 50-kg physical load.

Figure 3 shows that the configuration of pneumotachygrams of a standard

phrase with a physical load can be reproduced rather readily; however,

with large loads, 50 kg or more, phonated expiration is often interrupted

by one or two extra inspirations.

There was no appreciable change in resistance of respiratory tract during

inspiration with a load; during an ordinary expiration, without phonation,

it increased somewhat (apparently due to diminished cross section of respiratory tract with reduction of lung volume). There was a sharp increase

(about 20-fold) in respiratory tract resistance during speech, as compared

to nonphonated expiration, due to narrowing of the rima.

It is known that the lungs have a second function consisting of creating

pressure in the subchordal space to assure a flow of air through the rima

and vibration of vocal cords, in addition to their main function, i.e.,

exchange of gases. We know that there is a co-relation between level of

subchordal pressure, velocity of air flow and volume of sound during

continuous phonation (singing) in expiration in the volume of vital lung

capacity (VC)[10, 11].

80
As a result of this investigation, several changes were demonstrated in

time, velocity and volume parameters of pulmonary ventilation during speech,

interpretation of which is based on analysis of dynamics of subchordal

pressure and air flow through the rima.

In particular, the appearance of extra inspirations during speech with a

physical load is apparently attributable to the fact that, with increase

in static physical tension, there is a decrease in lung volume due to

contraction of thoracic and abdominal muscles. In addition, expiration is

associated with increasing mean, as well as maximum velocities of air flox^

against the background of reduced lung volume, as a result of which the

volume of air in the lungs is insufficient to implement the complete volume

of phonated expiration, which leads to extra inspirations that interrupt

the flow of speech.

Proprioceptive impulsation from receptors of muscles and ligaments of the

thorax, which is directed toward attaining the lung volume at which speech

usually begins and retention of the customary stereotype of phonated expiration, apparently has some significance as well.

The resistance of the respiratory tract is the integral index of aerodynamic

processes in the lungs and vocal tract during speech. Like other authors

[10], we observed a sharp increase therein during phonation, as a result of

constriction of the rima. This resistance was about 20 times greater than

total resistance of intrathoracic and extrathoracic respiratory tracts

during ordinary respiration.

Resistance of the larynx fluctuates over a wide range: 5-10 cm water/liter/s

when uttering consonants and up to 70-100 cm water/liter/s when uttering

vowels.

We observed fluctuations of resistance from 18 to 72 cm water/liter/s

during ordinary speech associated with rapid alternation of vowel and consonant sounds, against the background of a relatively stable mean leve] of

order of 44-62 cm water/liter/s at rest and with different physical load

levels. Consequently, it can be concluded that high intrathoracic pressure,

which aids in immobilization of thoracic and abdominal muscles during

static tension of postural muscles, does not have an appreciable effect on

laryngeal resistance, due to approximately equal increase in intrathoracic

pressure and velocity of air flow.

BIBLIOGRAPHY

1. Popov, V. A.; Simonov, P. V.; Frolov, M. V.; et al. ZH. VYSSH. NERVN.

DEYAT. [Journal of Higher Nervous Activity], Vol 16, 1966, p 974.

2. Luk'yanov, A. N., and Frolov, M. V. "Signals of Condition of Human

Operator," Moscow, 1969.

81
3. Kuznetsov, V. S., and Kurashvili, V. A. in: "Kosmicheskaya biologiya

i aviakosmicheskaya meditsina. Tezisy do'kl. na 4-y Vsesoyuzn. konf."

[Space Biology and Aerospace Medicine. Summaries of Papers Delivered

at the 4th All-Union Conference], Moscow—Kaluga, Vol 1, 1972, p 25.

4. Williams, C. E., and Stevens, E. N. AEROSPACE MED., Vo] 40, 1969,

pp 1369-1372.

5. Simson, L. Ibid, Vol 42, 1971, pp 1002-1006.

6. Comroe, J.; Forster, R.; and Dubois, A. "The Lungs. Clinical Physiology and Functional Tests," Moscow, 1961.

7. Frank, N.; Mead, J.; and Ferris, B. J. CLIN. INVEST., Vol 36, 1957,

pp 1680-1688.

8, Mead, J.; Bounuys, A.; and Proctor, D. ANN. N.Y. ACAD. SCI., Vol 155,

1968, pp 177-181.

9. Ladefoged, P. Ibid, pp 141-152.

10. Klatt, D.; Stevens, K.; and Mead, J. Ibid, pp 42-55.

11. Proctor, D. Ibid, pp 208-209.

82
UDC: 612.126+612.111.19].014.426

ELECTROLYTE CONTENT OF BLOOD AND POTASSIUM ION TRANSPORT IN ERYTHROCYTES OF

ANIMALS EXPOSED TO A STEADY MAGNETIC FIELD

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 63-67

[Article by C. K. Gerasimova and Z. N. Nakhil'nitskaya, submitted 1 Oct 75]

[Text] Technological progress is posing an increasingly acute question of

influence of a high-tension steady magnetic field (SMF) on the human body.

This problem is also a pressing one for physical laboratories and many

branches of industry. In recent years, there has been discussion in the

literature of the possibility of using high-power magnetic fields to protect

the crew of spacecraft from ionizing radiations in the course of prolonged

flights [1, 2]. The existing experimental data are indicative of the

biological activity of magnetic fields; however, few clearcut results have

been obtained. Several questions were overlooked by researchers. For this

reason, it is not yet possible to derive unequivocal conclusions as to

the nature and extent of SMF effects on the human body. In particular,

not enough work has been done on the question of SMF influence on electrolyte

metabolism in the entire organism and in the cell. Maintenance of constant

concentrations of alkaline metal ions is important to normal vital functions

of both the whole organism and its different systems and cells. At the same

time, we know that there is a decline of levels of potassium, sodium and

chloride ions in blood, with concurrent tendency toward increase in calcium

ions in human blood following 15-60-min local exposure to SMF of 1000 Oe [3].

Et has been reported that there is a reliable increase in excretion of potassium and sodium ions in urine of mice exposed to 14 kOe SMF for 24 h and

7.2 kOe for 96 h [4], as well as changes in potassium, sodium and calcium

ion levels in blood and other mouse organs after exposure to 5000 Oe SMF [5]

for 1-6 days, and in the blood of rabbits after exposure of the head to SMF

of 2000 and 4000 Oe [6]. It is assumed that strong magnetic fields affect

migration of sodium ions through biological membranes [7, 8].

Our objective was to determine the nature and extent of SMF influence on

concentration of potassium and sodium ions in blood, distribution thereof

in plasma and erythrocytes, blood pH and erythrocyte volume in animal

blood, as well as transfer of potassium ions through the erythrocyte membrane in in vitro experiments.

83
Methods

Male rats weighing 180-220 g, in a plexiglas box, were placed in the field

of an SP-15A electric magnet with flat parallel pole shoes 400x300 mm in

size. They were 100 mm apart. The magnetic field was virtually uniform

in the central part of the interpolar space 300x200 mm in size, and

voltage drop in the rest of the space did not exceed 15-20% of the level

in the middle. Voltage pulsation constituted 1.8%. The south pole was

referable to the top polar shoe. Field voltage was measured with a type

Ye-11-3 magnetic induction gage. The error factor of the instrument constituted ±(1.5+100/H)%, where H is force of the field (in Oe). Control

animals were kept in the same room as the experimental ones. The magnetic

field in the area of the control animals did not exceed 1.5 Oe. We conducted

six series of experiments differing in duration of exposure of animals to

the magnetic field (1, 3, 24 h and 15 days) and force thereof (1000 and

4500 Oe). In one of the series, the animals were exposed repeatedly to

4500 Oe SMF for 3 h daily, for 5 days. Blood was taken by decapitating the

animals. We assayed potassium and sodium ion content of blood and plasma

by flame photometry, erythroeyte volume according to the hematocrit index,

and blood pH on a micro-pH-meter. The tests were made at the early postexposure stages: 1 and 3 h after discontinuing exposure, and in the series

with 3-h exposure to 4500 Oe SMF after 5 days as well. We evaluated transport of potassium ions through the erythroeyte membrane according to the

values of coefficients Kab and Kba, which characterize transport of potassium

ions from plasma to the cell and from the cell to plasma. For this purpose,

we used radioactive potassium (

42

KC1 and "

2

K2C03). Tests were made on

eluted erythrocytes of white rats suspended in a mixture of buffer solution

and plasma (10:1 ratio). The erythroeyte suspension was put in a water bath

at 37° in a 4500 Oe magnetic field for 3 h. We determined the transport

coefficients during the 1st and 3d h of incubation in the SMF. For this

purpose, at the beginning of the 1st and 3d h of incubation, we added the

isotope to the test tubes with erythroeyte suspension at the rate of 7 uCi

per ml suspension, and then took samples every 20 min to estimate regression

of radioactivity of plasma, hematocrit index, potassium content in the

erythroeyte suspension and in the incubation medium. Radioactivity was

counted on a PST-100 unit. We .calculated the coefficient of potassium ion

transport from plasma to the cell, Kab, using the following formula:

ACp

~Cp~

KabAt,

where Cp is the initial concentration of plasma "

2

K, and ACp is change

thereof in time At. The slope of the absorption curve was calculated by

the least squares method. The coefficient of potassium ion transport from

the cell into plasma was calculated using the following formula:

v v ^R _L. 1-H 1

Ac

K p

ba = Kab : n + -5- • -7T- • -A2- Cq H Cq A t

where Kab is the transport coefficient in the plasma—cell direction; Cp

is mean potassium concentration of plasma during incubation period; Cq is

mean concentration of potassium in the cell during incubation period; ACp is

change therein in time At; H is hematocrit index.

84
Results and Discussion

Exposure to SMF induced changes in potassium and sodium ion content of the^

animals' blood and plasma. We could detect lowering of concentration of K*

and elevation of Na' in the blood and K" in plasma 1 hour after exposure to

3400 Oe SMF for 1 h. At this time, the K* and Na' levels in blood of experimental animals constituted 147.014.4 and 209±12 mg%, versus 162.5±2.4 and

178.2±2.2 mg%, respectively, in the control. K" content of blood plasma in

the experimental group of animals rose to 23±2.8 mg%.l h after exposure,

versus 16.3+1.7 mg% in the control. Some of the observed changes were transient. The electrolyte levels in blood reverted to initial values 3 h after

exposure, whereas blood plasma K' concentration still remained high. After

3-h exposure to 4500 Oe SMF, the blood of experimental animals showed a

decline of Na concentration. This was observed 1 h after exposure and

it persisted for the next 5 days. At this time, there were maximum changes

in Na" content. Na' concentration constituted 156.3±2.2 mg% on the 5th day

after exposure, versus 178.2±2.2 mg% in the control; it constituted 166±2.5

and 170±Q.2 mg% 1 and 3 h after exposure, respectively. We failed^to

demonstrate changes in blood K' content and blood plasma K' and Na* after 3-h

exposure. The changes in blood electrolyte content were less consistent

after exposure to 1000 Oe SMF.

After 1-h exposure, we observed a transient decline of blood Na" content.

1 h after exposure. Its concentration constituted 169+2 mg% in experimental

animals, versus 185.5±6.7 mg% in the control. The concentration of potassium

ions in blood and plasma did not exceed the range of control levels 3 h after

exposure. We failed to demonstrate deviations referable to the other indices

studied with such exposure. There were no cumulative effects when exposure

time was increased. On the contrary, after both 1- and 15-day exposure,

during the period of immediate after-effects, no change was demonstrated in

blood Na' content, although such a change was typical after 1-h exposure,

and this is indicative of the possibility of recovery of Na* content during

exposure. With increase in exposure time there was a tendency toward higher

K' content in plasma. Its level was 1.6 mg% above the control after 1-day

exposure. No changes were observed in blood and blood plasma K" content

with 15-day exposure. Cumulative effects were also lacking in the case

of repeated exposure. A study of changes in blood electrolyte content

following daily 3-h exposure to SMF of 4500 Oe for 5 days revealed that

the decline in blood Na" concentration observed immediately after the first

exposure does not progress thereafter with increase in number of exposures.

The differences between experimental and control animals leveled off, with

regard to Na' content of blood, after three and five exposures. At the same

time, differences in concentration of K* of blood appeared only after the

fifth exposure. They coincided in direction and magnitude with the changes

demonstrated 5 days after single 3-h exposure to a field of the same force.

We failed to demonstrate changes in plasma K" and Na" content after five

exposures. The concentrations of K" and Na" constituted 18±1.2 and 325+7.3 mg%,

respectively, in the control and 16+1.5 and 314+6.6 mg% in the experimental

group. The pH and erythrocyte volume in blood of experimental animals did

not undergo any changes. Only in the series of tests with 1-h exposure to
SMF of 4500 Pe did we observe a statistically reliable decrease in blood

erythrocyte volume 1 hour after exposure. It was transient and the level

reverted to normal in the 3d postexposure hour.

Experiments with incubation of erythrocytes in a SMF revealed that there is

no increase in gradient yield of potassium ions in the incubation medium

during exposure. Thus, after 1-h incubation in a 4500-Ce SMF, K' concentration in the incubation medium constituted 15.1±1.70 mg%, versus 14.8±0.38 mg%

in the control; after 3-h incubation the figures were 15.9±0.74 mg%, versus

15.1±0.05 mg% in the control. The results of estimation potassium ion transport through the membrane of erythrocytes incubated for 1 h and 3 h in a

4500-Oe SMF at 37°C indicate that the SMF does not affect transport of

potassium ions into the cell and from the cell into plasma. The Table

lists the coefficients characterizing transport of potassium ions through

the erythrocyte membrane. We see that with both 1- and 3-h exposure the

coefficients of potassium ion transport from plasma to cell and from cell

to plasma, as well as the overall flow of potassium ions in both directions,

do not differ from control values.

Potassium ion transport through erythrocyte membrane after exposure to

4500-Oe SMF varying in duration

Exposure time

(h)

Experiment

n = 9

1 Control

n = 9

Experiment

n = 6

3 Control

n = 6

"ab ba

K'concentration in

plasma(mgequiv/1

cells/h)

0,730+0,040

0,703+0,053

0,7G5±0,Of)9

0,774+0,035

0,034+0,002

0.033+0,004

0,035+0,005

0,033+0,002

4,34+0,410

4,10+0,310

4,07+0,231

3,85+0,013

K- flow

into cell

K* flow from

cell to plasma

(mg-equiv/1(mg-equiv/1

^ells/h) cel].s/_lil

3,44+0,230 3,05+0,175

3,45+0,198 3,00+0,104

3,27+0,450 3,11+0,393

3,20+0,114 2,94+0,114

Thus, the results of these experiments indicate that 1- and 24-h exposure

of animals to 1000-0e SMF does not elicit appreciable changes in concentration

of potassium and sodium ions in blood. An increase in force of SMF to 4500 Oe

is associated with some variability of changes in electrolyte composition of

blood. The reliable increase in plasma K* concentration and transient decrease in level thereof in blood should be considered the most distinct

changes in the case of 1-h exposure. With 3-h exposure, the most distinct

change is the decreased concentration of Na' in blood. Repeated and prolonged continuous exposure does not lead to summation of effects. The

demonstrated changes are not pathological in nature, and they do not exceed

the range of physiological fluctuations. The lack of changes, in our experiments, in coefficients of potassium ion transport through the erythrocyte

membrane does not rule out the possibility that SMF affects transmembr.ane

86
transfer of ions during exposure. To answer this question, special methodological approaches are needed that would not require long treatment of

the substrate after discontinuing exposure, when rapid recovery from

changes observed in the field is possible.

The pH and volume of blood erythrocytes did not undergo any changes.

BIBLIOGRAPHY

1. Trukhanov, K. A.; Ryabova, T. Ya.; and Morozov, D. Kh. "Active Protection of Spacecraft," Moscow, 1970.

2. Busby, D. E. SPACE LIFE SCI., Vol 1, No 1, 1968, p 23.

3. Vyalov, A. M., and Dukhanova, V. P. in: "Materialy 2-go Vsesoyuznogo

soveshchaniya po izucheniyu vliyaniya magnitnykh poley na biologicheskiye

ob"yekty" [Proceedings of 2d All-Union Conference on the Effects of Magnetic Fields on Biological Objects], Moscow, 1969, p 59.

4. Hanneman, G. D. in: "Biological Effects of Magnetic Fields," New York,

Vol 2, 1969, p 127.

5. Markuze, I. M.; Ambartsumyan, R. G.; Chibrikin, V. M.; et al. IZV. AN

SSSR. SER. BIOL. [News of the USSR Academy of Sciences. Biology Series],

No 2, 1973, p 281.

6. Abdullina, Z. M. "Biological Effects of Magnetic Fields on the Living

Organism," Frunze, 1975, p 119.

7. Blanchi, A.; Capraro, V.; and Gualtierotti, T. J. PHYSIOL. (London),

Vol 168, 1963, p 61.

8. Gualtierotti, T. PHYSIOLOGIST, Vol 7, 1964, p 150.

87
UDC: 612.119.014.482.2

HEMOPOIESIS IN DOGS EXPOSED TO LETHAL DOSES OF PROTONS WITH SHIELDED BONE

MARROW

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 67-70

[Article by G. F. Nevskaya, G. M. Abramova, Ye. V. Ginsburg, D. N.

Ishmukhametova,and A. S. Skorik, submitted 2 Dec 74]

[Text] At the present time it is unquestionable that shielding of part of

the bone marrow during exposure to acute radiation attenuates sharply the

biological effect of radiation. This is a pressing problem in order to

assure radiation safety of space missions.

In order to solve problems of space radiobiology, it is interesting to investigate the long-term effects of nonuniform irradiation by protons which,

as we know, are the main component of solar burst radiations.

Results and Discussion

Our studies are referable to the results of 6-year observation of 18 dogs

exposed twice to minimum absolutely lethal doses (350 rad) of protons at

a 45-day interval. Shielding of 10% of the bone marrow in the region of

the head (5 animals), 13% in the region of the chest (5), 5% in the abdominal

region (4) and 14% in the pelvic region (4 animals) resulted in survival of

the dogs.

In the acute period of radiation sickness the changes in all formed elements

of peripheral blood, with the exception of erythrocytes, were considerably

more severe in dogs exposed to radiation with the abdomen shielded. Thereafter, at longer intervals following irradiation, these differences gradually

levels off, although hemopoiesis remained deficient for several years in

animals irradiated with protection of the abdominal region. There were

still very marked differences in amount of elements studied 1.5 months after

exposure, in animals with shielded abdomen and in dogs in the other experimental groups. However, starting in the 3d month of observation, the differences became statistically unreliable. On the whole, over the entire

observation period, in all groups of dogs the leukocyte count did not reach

base levels, ranging from 60 to 85% for the first 3 years and holding at

the 70-90% level thereafter.

88
Interestingly enough, according to the data of N. K. Yevseyeva [3], in

healthy dogs of the same age maintained under the same conditions as our animals, the leukocyte count began to drop gradually when they reached 3 years

of age, and by the age of 4-5 years it constituted 65-75% of the initial

level. On the basis of these data, it can be stated that as early as 2 years

after irradiation the leukocyte level in irradiated dogs in our experiments

was within the physiological range. Nevertheless, the total number of these

cells in peripheral blood does not determine leukopoiesis in the organism,

and there are quite a few signs that suggest it did not revert to the initial

level in irradiated animals.

First of all, we found that absolute lymphopenia and neutropenia persisted,

even 5-6 years after irradiation of the dogs, and animals exposed to radiation with the abdomen shielded presented no more than 75% lymphocytes in

blood at any of the examination times. Along with quantitative changes,

there were deviations in morphological structure of leukocytes. We found

segmented lymphocytes and monocytes, hypersegmented neutrophils, binuclear

cells or cells with vacuolized nucleus and protoplasm, as well as other degenerative forms of leukocytes. The thrombocyte content of blood did not

revert to the initial level either, although some of the tests revealed that

the number of such cells in animals of some groups was close to the background

values. The dogs gradually developed anemia in the course of the observation

period (see Table).

Red blood cells indices in dogs 4.5 years after two exposures to proton

radiation in a dosage of 350 rad with local shielding of the body (M+m)

Red blood cell Numerical value of indices

index before radiation after radiation

P

Erythrocytes:

absolute

%

Hemoglobin

Color index

7,1+0,22

100

13,8+0,1!

0,58+0,017

(i.2+0,2

87+1,7

12,9+0,-10

0,02+0,027

.-;o,02

r 0,05

- 0,05

Changes in medullary hemopoiesis occurred concurrently with those in peripheral blood.* While the composition of bone marrow in dogs exposed to radiation with shielded head, chest and pelvis did not show an essential difference

from the initial composition after termination of the acute period of radiation sickness, in animals exposed to radiation with shielding of the abdomen

there was impairment of proportions between cellular elements on the myelogram (Figure 1). There was severe irritation of the reticular storma of bone

marrow, as indicated by the significant increase in number of reticular cells,

*M. P. Kalandarova conducted the observations for the first 3 years.

89
plasmacytes and monocytes (16.8%). There was also an elevated lymphocyte

level. There was also a significant increase in erythroid stem cells (to

19.2). Thereafter, for over 3 years of observation, these differences in

medullary hemopoiesis persisted in animals exposed to radiation with the

abdomen shielded and in animals of other experimental groups. However,

the situation changed 5.5 years after irradiation. While functional activity

remained at the same level at this time in bone marrow of animals exposed

to radiation with the abdomen shielded, there was a perceptible change in

dogs with shielded thorax, head and pelvis. As a result, the bone marrow

findings were identical in animals of all groups. As can be seen in

Figure 1, which illustrates comparative hemopoiesis in dogs irradiated

with shielding of the chest and abdominal region, the quantitative proportions of cellular elements on the myelograms were markedly altered. There

was a sharp decrease in red stem cell level with relatively unchanged

white stem cell level and the leuko-erythroblast index was greater than 2.

We observed irritation of reticular stroma and an increase in levels of

lymphoid elements. There were fewer than 2% young forms of granulocytes.

Analogous changes were demonstrated in dogs exposed to radiation with the

head and pelvis shielded.

/3\S5

Background t',s mo

Figure 1. Bone marrow of dogs at different times following twofold exposure to protons in a dosage of 350 rad,

with shielding of the chest (1) and abdomen (2)

Comparative dynamics of changes in bone marrow indices of the dogs, as

compared to the initial data, are illustrated in Figure 2, which shows that

in the presence of significant depression of functional activity of erythroblasts there is marked proliferation of reticular stromal cells. As we

know, intensified proliferation of reticular cells, with limited capability

for differentiation thereof, can create the conditions for development of

leukemia [1, 2, 4-7, 9].

It is assumed that, in the case of exposure to nonuniform radiation, there

is no excessive proliferation of reticular cells because of preservation of

some of the hemopoietic elements. Attenuation of the leukemogenic effect

in the case of irradiation with shielding of bone marrow is usually

90
considered in relation to the foregoing. It is believed that when bone

marrow foci are protected restoration of hemopoiesis occurs primarily due

to preservation of stem cells under the shield, whereas in the case of

total-body irradiation regeneration of blood occurs at the expense of surviving but damaged cells. However, it should be borne in mind that shielded

bone marrow functions like a compensatory site only in the acute period of

radiation sickness. At the later stages, there is inevitable resumption

of activity of hemopoietic tissue in the irradiated parts of the body. Since,

according to current conceptions, disturbances referable to the chromosomal

system of formed blood elements are the pathogenesis in development of

leukemia, there are no grounds to expect elimination of the leukemogenic

effect in the case of nonuniform irradiation.

430

WO

370

3W

310

280 CO

01

*J 250

^220

O 190

H

m

S 130

^100

-

1 w

r"

0,12 3,5 5,5

Figure 2. Formed bone marrow elements in dogs following two-fold

exposure to proton radiation in a dosage of 350 rad with

shielding of the head (solid line), chest (dash line),

abdomen (dotted line) and pelvis (dash-dot line)

As we know [9], in spite of the predominantly nonuniform type of irradiation

of Japanese victims of atomic explosions, there was a higher incidence of

leukemia. In our experiments, no development of leukemia was observed in

91
dogs over the 6-year follow-up period, in spite of the fact that they were

exposed to doses known to be leukomogenic. Probably this is attributable

to the natural insusceptibility of these animals to this disease. Nevertheless, hypoplastic hemopoiesis with marked proliferation of the reticular

stroma, which they did develop, could be equated, in our opinion, with

a preleukemia state in man. It should be noted that such a hemopoietic

reaction was encountered for 7-9 years in Hiroshima and Nagasaki among

individuals exposed to radiation in doses of 100-500 rad [10].

The obtained data indicate that the bone marrow should apparently be considered a critical organ, not only in the acute period of radiation sickness,

but at the long postradiation term after exposure to a range of doses that

elicits primarily damage to hemopoietic organs.

BIBLIOGRAPHY

1. Bogoyavlenskaya, M. P., and Malanina, V. N. MED. RADIOL. [Medical

Radiology], No 11, 1966, pp 43-49.

2. Gus'kova, A. K., and Baysogolov, G. D. "Radiation Sickness in Man,"

essays, Moscow, 1971.

3. Yevseyeva, N. K. in: "Otdalennyye posledstviya luchevykh porazheniy"

[Long-Term Sequelae of Radiation Lesions], edited by Yu. I. Moskalev,

Moscow, 1971, pp 107-113.

4. Kurshakov, N. A. VESTN. AMN SSSR [Vestnik of the USSR Academy of

Medical Sciences], No 4, 1958, pp 27-32.

5. Krayevskiy, N. A. "Essays on Pathological Anatomy," Moscow, 1957.

6. Krayevskiy, N. A.; Strel'tsova, V. N.; and Moskalev, Yu. I. MED. RADIOL.,

No 7, 1962, pp 68-71.

7. Krayevskiy, N. A., and Litvinov, N. N. ARKH. PAT. [Archives of

Pathology], No 8, 1959, pp 3-16.

8. Krayevskiy, N. A.; Nemenova, N. M.; and Khokhlova, M. 0. "Pathological

Anatomy and Problems of Pathogenesis of Leukemia," Moscow, 1965.

9. (Khirose), F. in: "Sequelae of Atomic Bomb Explosion in Hiroshima,"

Moscow, 1960, pp 56-78.

10. Kawalshi, K. in: "Investigation of Sequelae of Nuclear Explosions,"

Moscow, 1964, pp 144-155.

92
UDC: 574.682:576.8:635.116

INVESTIGATION OF CONCOMITANT MICROFLORA IN PROLONGED SUBSTRATE-FREE

CULTIVATION OF BEET PLANTS

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 71-74

[Article by L. S. Yunusova and N. A. Drugova, submitted 26 Jul 74]

[Text] Studies are being pursued of the material balance of plants, when

cultivated by the substrate-free method, as well as the possibility of using

the same nutrient solution, with no changes, for long-term cultivation of

plants, for the purpose of including higher autotrophs in closed ecological

systems. However, in experimental ecological systems, such cultivation

cannot be based solely on providing balanced nutrient media without taking

into consideration vital functions of microflora. For this reason, the

question of correlations between higher plants and microorganisms is an

important one to ecology of bioregenerative systems.

In biological systems of life support with higher plants, their bacterial

composition will influence formation of the environment of sealed objects

as well. Consequently, we must study more than the role of microorganisms

in development of plants.

In spite of the fact that there are a number of current works dealing with

amounts of microorganism surrounding the root systems of plants, there is

still no clearcut conception as to whether it is beneficial for the plants

to have a large amount of microorganisms on the root surface and whether

there is a certain population level that provides for an optimum correlation

between the plants and microflora [2].

Our objective was to investigate the dynamics of microorganism population

size in the case of long-term substrate-free cultivation of beet plants,

as well as their qualitative and quantitative composition.

Methods

Bordeau variety of beets were cultivated by the hydroponic method in two

permanent nutrient solutions differing in salt concentration: 1) Chesnokov

93
solution; 2) balanced solution of macroelements in 10-100 times lower concentration ("aqueous background"). In the course of the experiment, the

solutions were constantly adjusted with regard to elements of mineral nutrition in accordance with consumption thereof by the plants. The initial

material for the cultures were samples of nutrient solutions in which plants

had been cultivated, as well as washings from the roots. We took samples

every 2 weeks and inoculated them on nutrient media. In order to determine

the amount of bacteria we used the Koch cup method. We used meat-peptone

agar (MPA) and cabbage medium No 19, which is recommended as the optimum

medium for epiphytic microflora [3], as the nutrient media.

Elective media were used to study specific groups of microorganisms. Actinomycetes were studied on starch-ammonia agar and fungi on acidulated wort agar

(WA), with a pH of 6.0. We used the method of azotobacter growth around

rootlets in concentrated Ashby medium for demonstration of aerobic nitrogenfixing microorganisms. We also studied oligonitrophil forms on unconcentrated

Ashby medium, and sporulated ones on MPWA (MPA and WA in a ratio of 1:1).

The method of maximum dilutions in liquid nutrient media was used for group

analysis of the following physiological groups of microorganisms: 1) ammonification bacteria on meat-peptone broth; 2) denitrifying bacteria on Gil'taya

medium; 3) anaerobic nitrogen-fixing bacteria on organic nitrogen-free medium

of Vinogradskiy; 4) cellulose anaerobes on Omelyanskiy medium with filter

paper; 5) cellulose aerobes on medium proposed by Yu. M. Voznyakovskaya;

6) nitrifying bacteria on inorganic Vinogradskiy medium.

We then counted the number of microorganisms using the McCready table. Conventional techniques were used to isolate microorganisms in pure cultures

and to assay them [4].

Results and Discussion

It is apparent from the results obtained that the bacterial number, determined from growth of microorganisms on MPA increases in both nutrient solutions

toward the period of intensive increment of beetroots, i.e., by the 91st day,

and then it diminishes by harvesting time (Figure 1); there are more microorganisms in Chesnokov solution than in the "aqueous" variant. As was to

be expected, there were many more root-related microorganisms, as compared

to total bacteria in both nutrient solutions, but the nature of their

development was the same in all variants.

21 .15 <<9 63 77 51 105 113 133

Figure 1.

Dynamics of microorganism population size

during long-term substrate-free cultivation

of beets. Here and in Figures 2-4:

x-axis, time (days); y-axis, number

of microorganisms (millions per ml solution and g roots). Solid line, root

microflora; dash line, microflora in

Chesnokov solution; dash-dot line, microflora in "aqueous" variant

94
Identification of microorganisms according to physiological groups revealed

that there were nitrogen-fixing, ammonifying and denitrifying organisms, as

well as oligonitrophils, aerobic cellulose-decomposing organisms and a small

amount of fungi. We failed to demonstrate nitrifying and sporogenic microorganisms .

As can be seen in Figure 2, there is a decrease in number of oligonitrophils

in solutions on the 49th day and, at about the same time, there is appearance

of a representative of bacteria that fix atmospheric nitrogen, the azotobacterm

which is apparently related to temporary decrease in nitrogen content of the

nutrient medium. However, after the increase in oligonitrophils on the roots

by the 49th day their number remains the same thereafter. Unlike oligonitrophils, ammonifyers and denitrifyers in nutrient solutions present a

sharp increase by the end of the vegetation period (Figures 3 and 4)". But

on the roots the amount of denitrifying bacteria diminishes in the course

of development of the plants, while that of ammonifying bacteria increases.

A study of denitrifying microorganisms revealed that only some of them are

genuine denitrifyers. Cellulose-decomposing aerobic microorganisms began to

appear in the middle of the vegetation period, and this was probably related

to the start of necrosis of root hairs, and toward the end of the vegetation

period a negligible amount of fungi also appeared.

W'r

w

W

10

I

0

/ ~~^—~-

\

\

3_.

Figure 2.

Change in amount of oligonitrophils

during vegetation of beets (millions

per ml solution and gram roots)

21 35 49 6J 77 91 WS '19 133

It should be indicated that we failed to observe any particular differences

in development of garden beets on the nutrient solutions mentioned, but there

wus a difference in amount of nutrients in the leaves and roots.

There was more sugar in the leaves of plants cultivated on an "aqueous

background" than in beets grown on a mineral background, but less starch.

The same pattern is more pronounced in the roots. Cellulose content of the

leaves and roots does not differ in the variants. In young plant roots

cultivated in Chesnokov solution there was 2-3 times more ascorbic acid.

The differences in nutrient content result in specific accumulation thereof.

In plants cultivated in Chesnokov solution, carbohydrates are present mainly

in the form of starch, and in those raised in a water background, in the

95
form of monosaccharides and disaccharides. Accumulation of ascorbic acid

follows the same patterns as were noted in levels thereof.

/I'

•,ns

/!' /-1

//i m' bv A /' i

;os

w

\ \ / 1

\ /

0

1 1 V,—' ' '

L

'

?7 35 M 83 77 91 '05 119 133

Figure 3.

PI 35 M (S3 77 31 105 'W '33

Figure 4.

Development of ammonifying bacteria Development of denitrifying bacteria

during growth of beet plants during growth of beet plants

(billions per ml solution and gram roots)

Perhaps the above difference in quality of harvest in the experimental

variants also affects the nature of accumulation of concomitant microflora.

Confirmation of this aspect requires further parallel study of the quantitative and qualitative composition, dynamics of microflora concomitant in

higher plants, and direction of biosynthesis of nutrients.

We made an identification of the dominant forms of microorganisms isolated

in the course of prolonged cultivation of beets. We found that the majority

of bacteria were referable to Pseudomonas and Mycobacterium. Representatives of the genera Bacterium, Micrococcus, Mycococcus, Chromobacterium and

Pseudobacterium are also encountered.

BIBLIOGRAPHY

1. Krasil'nikov, N. A. "Microbiology of Soil and Higher Plants," Moscow, 1958.

2. Samosova, S. M. in: "Mikroorganizmy pochvy i ikh vzaimootnosheniya s

vysshimi rasteniyami" [Soil Microorganisms and Their Correlations With

Higher Plants], Kazan', 1971, pp 3-12.

3. Voznyakovskaya, Yu. M. "Plant Microflora and Harvest," Leningrad, 1969.

4. Krasil'nikov, N. A. "Guide to Bacteria and Actinomyctes," Moscow—

Leningrad, 1949.

96
METHODS

UDC: 612.014.47-064].001.57

PHYSIOLOGY OF ANTIORTHOSTATISM

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 75-76

[Article by K. L. Geykhman and M. R. Mogendovich, submitted 29 Jul 75]

[Text] It is extremely difficult to find experimental solutions to physiological problems of weightlessness, since it is impossible to fully

simulate weightlessness on earth. Nevertheless, some advances have been

made in this area [4].

Among the methods of modeling weightlessness, which are used to investigate

the dynamics of physiological systems and, first of all, the cardiovascular

system, particular importance is now being attributed to the antiorthostafic

[head down] position. The "head down" position had occasionally been used

in pathophysiological experiments on animals as a unique functional test

for evaluation of circulation in man [28]. A semblance of this position

is used in surgery (Trendelenburg position). Until recently, the "head down"

position had been only considered as a methodological procedure of little

importance. This question remained little studied in space physiology as

well. Yet the field of antiorthostatism is of basic importance to the

solution of a number of problems of normal and pathological physiology [29].

Tests using a tilted table have recently been adopted in experimental

physiology at English universities [44].

We began to use this position in 1962 to simulate accelerations and weightlessness in man, and we introduced the corresponding concept of "antiorthostatism." And we make a distinction between passive and active antiorthostatic positions. Their mechanisms are somewhat different: the passive

position is related to muscular relaxation, whereas the active one involves

voluntary muscular tension, particularly with reference to the hands, for

example in hand stands.

Physiology of antiorthostatics was investigated extensively and on a theoretical basis in the Perm' Laboratory for the last 12 years [6, 7, 9-16, 24,

36-41]. In the compendiumsthat have been published since 1968, "Biomedical

Studies in Weightlessness" [32] and "Physiology in Space Environment" [43],

nothing was stated about physiological research on antiorthostatics, and

97
even this term did not yet exist. Subsequently, R. M. Bayevskiy [5] studied

antiorthostatism, and he considered it a valuable prognostic test. Yugoslav

authors [42] used the "head down" vertical position for 60 s and recorded

indices of the EKG, velocity of pulse wave and rheoencephalography. Changes

m the sensory system are studied in weightlessness [3, 27]. The changes

in various parameters of circulation, which occur in weightlessness in

astronauts [25, 26], are consistent with these experimental data. Thus, in

weightlessness there is redistribution of blood and increased filling of

venae cavae, right atrium, vessels in the pulmonary circulation and left

atrium. Ye. A. Kovalenko [26] writes: "... cosmonauts report, virtually

always when in weightlessness, a sensation of blood rushing to the head,

heaviness of the head, as well as some hyperemia of the facial integument

and sclera. We consistently observed analogous findings in antiorthostatic

position, as well as some slowing of the pulse [12].

As a result of gravitational redistribution of blood and resulting neurohumoral, somatic and vegetative reactions, depressor reflexes develop from

receptors of the sinocarotid zone, Bainbridge reflex from the venae cavae,

etc. This is indicative of similarity of the mechanism of parasympathetic

influences in reactions of the organism to weightlessness and antiorthostatic

position of the body.

The combination of antiorthostatic position and prolonged hypokinesia is

of particular significance to the study of the weightlessness problem. A

xarge team of authors [8, 17] published several papers concerning a 30-day

experiment with simulation of the physiological effects of weightlessness,

and they concluded that "an antiorthostatic position with a -4° tilt is a more

adequate model of weightlessness than the ordinary horizontal position" [17].

A. V. Beregovkin and V. V. Kalinichenko [2], who studied reactions of the

cardiovascular system in antiorthostatic position with 30-day hypokinesia,

demonstrated quite moderate changes in circulatory functions. Thus, prolonged hypokinesia in an antiorthostatic position as a simulation of weightlessness with regard to hemodynamics requires further research in the aspect

of reflex interaction of systems of the organism [18, 19, 26, 31]. The

resilience of the organism with respect to gravitational loads is so great

that with adequate conditioning there are adaptational reactions to antiorthostatic positions as well [12]. The conditioning effect of the antiorthostatic position has been confirmed by D. A. Alekseyev et al. [1]. But

the position of the feet is not usually taken into consideration in the

antiorthostatic position. Yet the feet are a unique reservoir which can

stare 500-800 ml blood, or from which the same amount can flow. And this

atfects systemic hemodynamics. The same is observed in the cuff test of

Shval m [35] and other methods of artificially altering blood delivery to

the legs. Underestimation of the effect of foot position in antiorthostatic

poses could lead to fallacious interpretation of levels of minute volume and

other hemodynamic indices.

On the basis of these and other data [41], we have suggested that the antiorthostatic position be combined with elevation of the legs, which should

increase the effect of simulating weightlessness. This methodological

98
innovation consists of the following: we used antiorthostatic positions

varying in tension on a turning table, not only with the legs straight

(pose No 1) but with legs flexed at 30-35° on a footrest (pose No 2). We

obtained new data concerning different changes in man in this variant of

postural and vegetative reactions [16, 20-22, 33, 34]. We also investigated

the distinctions of kinesthesia [20], changes in skin and internal ["deep"]

temperature [20], oxygenation of blood [22] and sensibility of the acoustic

analyzer [23] in pose No 2.

As we see, the range of problems that are being solved by the method and

theory of antiorthostatic modeling of weightlessness is widening more and

more. The central problem with regard to research on the biological effects

of gravitation is not so much to technically refine recording of physiologies!

phenomena as to provide pathophysiological interpretation thereof [26, 30],

The question of using data obtained from antiorthostatic experiments for

the screening of cosmonauts and development of preventive measures requires

further investigation.

BIBLIOGRAPHY

1. Alekseyev, D. A.; Yarullin, Kh. Kh.; Krupina, T. N.; et al.

KOSMICHESKAYA BIOL. [Space Biology], No 5, 1974, pp 66-72.

2. Beregovkin, A. V., and Kalinichenko, V. B. Ibid, No 1, pp 72-77.

3. Bokhov, B. B.; Kornilova, L. N.; and Yakovleva, I. Ya. Ibid, No 1, 1975,

pp 51-55.

4. Barer, A. S.; Savinov, A. P.; Severin, G. I.; et al. Ibid, pp 41-47.

5. Bayevskiy, R. M. FIZIOL. ZH. SSSR [Physiological Journal of the USSR],

No 6, 1972, pp 819-827.

6. Berg, M. D. in: "Eksperimental'nyye issledovaniya po fiziologii,

biofizike i farmakologii" [Experimental Research on Physiology, Biophysics

and Pharmacology], Perm', Vyp 6, 1966, pp 59-65.

7. Idem, "Postural and Vegetative Reflexes of the Cardiovascular System

as Related to Age," candidatorial dissertation, Perm1, 1967.

8. Voskresenskiy, A. D.; Yegorov, B. B.; Pestov, I. D.; et al.

KOSMICHESKAYA BIOL., No 4, 1972, pp 28-32.

9. Geykhman, K. K. in: "Motorno-vistseral'nyye refleksy i smezhnyye

problemy" [Motor and Visceral Reflexes and Related Problems], Perm', 1962,

pp 53-63.

10. Idem, in: "Eksperimental'nyye issledovaniya po fiziologii, biofizike i

farmakologii," Perm', Vyp 5, 1963, pp 175-184.

99
11. Idem, Ibid, Vyp 6, 1967, pp 69-67.

12. Idem, "The Most Important Vegetative Changes in Man in Antiorthostatic

Position," candidatorial dissertation, Perm', 1965.

13. Geykhman, K. L., and Mogendovich, M. R. in: "Problemy kosmicheskoy

meditsiny" [Problems of Space Medicine], Moscow, 1966, pp 112-113.

14. Idem, in: "Aviatsionnaya kosmicheskaya meditsina" [Aerospace Medicine],

Moscow, Vol 1, 1969, pp 133-136.

15. Idem, "Nauch. trudy Perm. med. in-ta" [Scientific Works of Perm'

Medical Institute], Vol 95, Vyp 9, 1969, pp 48-63.

16. Idem, in: "Teoriya i praktika fizvospitaniya i sporta" [Theory and

Practice of Physical Education and Athletics], Perm', 1975, pp 83-86.

17. Genin, A. M., and Kakurin, L. I. KOSMICHESKAYA BIOL., No 4, 1972,

pp 26-28.

18. Georgiyevskiy, V. S. in: "Fiziologicheskiye problemy detrenirovannosti"

[Physiological Problems of Deconditioning], Moscow, 1968, pp 64-77.

19. Idem, in: "Eksperimental'nyye i kliniko-fiziologicheskiye issledovaniya

motorno-vistseral'noy regulyatsii" [Experimental and Clinicophysiological

Studies of Motor and Visceral Regulation], Perm', 1971, pp 86-89.

20. Gubman, L. B.; Komin, S. V.; and Petrov, B. V. in: "Vozrastnyye

osobennosti dvigatel'nykh i vegetativnykh funktsiy i ikh vzaimodeystviye

pri razlichnykh vidakh myshechnoy aktivnosti" [Age-Related Distinctions

of Motor and Autonomie Functions and Interaction Thereof in the Course

of Various Types of Muscular Activity], Kalinin, 1973, pp 123-172.

21. Gubman, L. B. in: "Teoriya i praktika vizvospitaniya i sporta," Perm',

1975, pp 89-90.

22. Gubman, L. B., and Petrov, B. V. in: "Nauchnyye osnovy fizicheskoy

kul'tury" [Scientific Bases of Physical Culture], Kalinin, Vyp 2, 1974,

pp 12-28.

23. Zubova, A. S. in: "Teoriya i praktika fizvospitaniya i sporta," Perm',

1975, pp 112-113.

24. Kolychev, V. P., and Petrenev, A. G. in: "Eksperimental'nyye

issledovaniya po fiziologii, biofizike i farmakologii," Perm', Vyp 7,

1967, pp 103-106, 176-178.

25. Kas'yan, I. I.; Kopanev, V. I.; and Yazdovskiy, V. I. in: "Nevesomost'"

[Weightlessness], Moscow, 1974, pp 89-105.

100
26. Kovalenko, Ye. A. Ibid, pp 237-278.

27. Kitayev-Smyk, L. A. KOSMICHESKAYA HLOL., No 5, 1967, pp 79-83.

28. Kudenko, M. V., and Chirkin, M. D. in: "Voprosy aviatsionnoy meditsiny"

[Problems of Aviation Medicine], Moscow, 1936, pp 24-52.

29. Mogendovich, M. R., and Temkin, I. B. "Analyzers and Internal Organs,"

Moscow, 1971.

30. Moskalenko, Yu. V.; Vanshteyn, G. B.; and Kas'yan, I. I. "Intracranial

Circulation in the Presence of Accelerations and Weightlessness, Moscow,

1971.

31. Mikhaylov, V. M.; Georgiyevskiy, V. S.; Petukhov, B. N.; et al. "Trudy

Perm. med. in-ta," Vol 103, 1971, pp 76-81.

32. Parin, V. V. (editor) "Mediko-biologicheskiye issledovaniya v

nevesomosti" [Biomedical Studies in Weightnessness], Moscow, 1968.

33. Petrov, B. V. in: "Teoriya i praktika fizvospitaniya i sporta,"

Perm', 1975, pp 126-127.

34. Sidorov, N. I. Ibid, pp 141-142.

35. Simonenko, V. V., and Pekshev, A. P. "Trudy Perm. med. in-ta," Vol 103,

1971, pp 92-96.

36 Khmeleva, S. N. in: "Voprosy fizkul'tury i sovershenstvovaniye

uchebnogo protsessa" [Problems of Physical Culture and Upgrading the

Educational Process], Volgograd, 1969, pp 245-247.

37 Idem "Correlation Between Reactions of the Cardiovascular System and

Muscle Tonus Under the Influence of Gravitational Perturbanc.es ^ in

Athletes," author abstract of candidatorial dissertation, Perm , 1971.

38. Chuvayeva, G. Z. in: "Eksperimental'nyye issledovaniya po fiziologii,

biofizike i farmakologii," Perm', Vyp 6, 1965, pp 54-58.

39. Idem, Ibid, Vyp 7, 1967, pp 42-46.

40. Shchurov, V. A. Ibid, pp 94-98.

41. Idem, "Functional Study of Age-Related Distinctions of Blood Delivery

to the Human Limbs," candidatorial dissertation, Perm', 1969.

42. Radovic, A. REV. MED. AERONAUT., Vol 12, No 45, 1973, pp 71-74.

43. "Physiology in Space Environment," Washington, 1968.

44. Andrew, B. L. (editor) "Experimental Physiology," London, 1972.

101
BRIEF REPORTS

UDC: 612.017.1-06:629.78

HETEROPHILIC ANTIBODIES AND COMPLEMENT ACTIVITY OF RAT BLOOD SERUM AFTER

FLIGHT IN KOSMOS-605 SATELLITE

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 76-78

[Article by V. V. Portugalov, A. A. Ivanov and V. N. Shvets, submitted

16 Dec 74]

[Text] Prolonged stays of animals and man in a sealed space are associated

with reduction [simplification] of automicroflora, and this could lead to

reduction of the immunocompetent system and impairment of natural immunity

[1]. Hypodynamia is another factor of space flights that lowers imunological

reactivity [2]. Immunological reactions are usually mediated in the organism

through humoral factors: specific (antibodies) and nonspecific (blood serum

complement)[3]. The levels of heterophilic antiboides in peripheral blood

(antibodies to sheep erythrocytes) are consistent with the capacity of

lymphoid tissue cells to produce antibodies.

There is increased interest in complement due to expansion of conceptions

about its involvement in processes of inflammation, blood clotting, immune

response, etc. [4]. Determination of complement activity of blood serum

offers an idea about the condition of the complement system.

The high sensitivity of both indices to the organism's response to Stressors

[5] was the reason for use thereof in studies of animals used in space

flights.

Methods

We studied serum samples from 26 experimental and 17 control rats. We

formed four groups of experimental animals: those that had spent 22 days in

flight on Kosmos-605, examined on the 2d (1st group) and 27th (2d group)

postflight days; the 3d and 4th groups consisted of animals kept under

simulated flight conditions (with the exception of weightlessness and

accelerations) for 22 days, and they were examined on the 2d and 27th days

after this.

102
We took samples of serum from control aivinals and tested it on tho sau:e day*

as experimental animals. We evaluated the level of serum cottpl.etr.ent ao.tiw,y

in units of 50% hemolysis (CH50). Presence of agglutinin antibodies to

sheep erythrocytes (0.5% erythrocyte suspension) was demonstrated in

inactivated serum using the microtitrator of the Takachi system, starting

with a 1/2 dilution.

Results and Discussion

On the 2d postflight day there was a significant, though statistically unreliable (t = 1.62), increase in blood serum complement activity (see Table).

On the 27th postflight day, there was normalization of complement level.

The animals in the concurrent ground-based experiment showed a similar

effect on complement level.

Effects of space flight factors on complement and heterophilic antibody levels

in rat blood serum

Animal

group_

1st

2d

3d

4 th

Subgroup

Serum compl,

activity,

CH50, ml

Hemagglutinins

incidence

Animals examined on 2d

postflight day

Vivarium control

Animals examined on 27th

'post flight day

Vivarium control

Animals in ground-based

concurrent experiment

(2d postexperiment day)

Vivarium control

Animals in ground-based

concurrent experiment

(27th postexperiment day;

Vivarium control

102,3+13,9

G8,2±14,7

82,3±7,2

80,4±8,5

102,1 ±8,2

81,1 ±4,3

08,3-4-10,2

85,0+13,3

0,8

3/3

l/'C

5/5

1/0

5/0

3/0

3/3

mean

intensity

2-!-

2-i-

<2

Note: The number of animals with positive reaction is shown in numerator

and number of animals in the group is given in the denominator.

We observed a decrease in hemagglutinin antibody content in all groups of

experimental animals. We shall not discuss the statistical significance of

this finding because of the small number of animals in the groups. At the

same time, it should be noted, that minimum levels of antibodies are

demonstrable in the recovery period in the 2d and 4th experimental groups,

according to incidence of demonstration.

103
In our opinion, the same mechanism may be the basis for increase in serum

complement activity and decrease in amount of heterophilic antibodies.

Myeloid cells mature faster under the influence of the extreme space flight

factors, as demonstrated morphologically [6]. In turn, this could lead to

accelerated functional maturation of myeloid cells and discharge into the

blood stream of one of the products they produce, i.e., complement components

[4]. Probably the higher cell metabolism results in a larger amount of

products of tissular decomposition that are bound in the organism by antitissular antibodies that are similar to natural hemagglutinins. The formed

antigen-antibody complex binds complement, and as a result there is rapid

normalization of its level in blood when the extreme factor is eliminated.

We observed comparable effects previously (higher complement level and

fewer antitissular antibodies) with regard to factors that are components of

extreme space flight factors: hypokinesia [7] and radiation [8].

Partial reduction of the immunocompetent system with simplification of automicroflora, as a result of staying in a closed space [1], may be another

cause of decrease in heterophilic antibodies. The latter, along with hypodynamia, is probably an important factor leading to lowering of heterophilic

antibody level in the animals of the ground-based experiment.

We cannot derive a conclusion about the immunocompetent system of rats

involved in the space flight on the basis of a single test, though it is

quite informative. Our findings are indicative of the need for comprehensive

examination of animals when studying their immunological reactivity.

To sum up the results submitted above, it can be stated that a 22-day stay

onboard Kosmos-605 satellite led to elevation of complement level in rat

blood serum and more persistent decrease in amount of heterophilic antibodies.

Complement activity of blood serum was restored on the 27th postflight day,

whereas the heterophilic antibody content was still low at this time.

BIBLIOGRAPHY

1. Lebedev, K. A., and Petrov, R. V. USPEKHI SOVR. BIOL. [Advances in

Modern Biology], Vol 71, 1971, pp 234-252.

2. Galaktionov, V. G., and Ushakov, A. S. KOSMICHESKAYA BIOL. [Space

Biology], No 5, 1969, pp 43-47.

3. Mayer, M. SCI. AMER., Vol 229, No 5, 1973, pp 54-66.

4. Lachmann, P. J. in: "Clinical Aspects of Immunology," Oxford 1975

pp 323-364.

5. Reznikova, L. S. "Complement and Its Significance in Immunological

Reactions," Moscow, 1967.

104
6. Shvets, V. N., and Kirvenkova, N. P. KOSMICHESKAYA BIOL., No 3, 1976,

pp 47-52.

7. Portugalov, V. V.; Ivanov, A. A.; and Shvets, V. N. Ibid, No 2, 1976,

p 84.

8. Ivanov, A. A. in: "Autoantitela obluchennogporganizma" [Autoantibodies

of the Irradiated Organism], Moscow, 1972, p 21.

10!
UDC: 629.78:612.014.482-087

MEASUREMENT OF RADIATION DOSES IN THE SOYUZ-16 SPACECRAFT

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 78-79

[Article by Yu. A. Akatov, Ye. Ye. Kovalev, V. M. Petrov, M. V. Tel'tsov

and V. I. Shumshurov, submitted 30 Oct 75]

[Text] The Soyuz-16 spacecraft was put into orbit with the following

parameters: HTT = 177 km, Ha = 225 km, i = 51.8°, on 2 December 1974 in

accordance with the program of preparations for the joint mission of Soyuz

and Apollo spacecraft. During the flight, the orbit was corrected and

became close to a circular one with an altitude of -220 km.

These orbital parameters determined the characteristics of the radiation

conditions on the path and in the craft, as well as the specifications

with regard to the system of monitoring them. An R-15 dosimeter was installed on Soyuz-16 to measure the integral dose of cosmic radiation; it

provided the necessary information for the ground-based radiation safety

service. The instrument was equipped with an ionization chamber of plexiglas that was filled with argon. During operation, the ionization current

in the chamber was converted into pulses, the number of which is proportionate

to accumulated dosage. The precision of dose readings in the range of

0.0125:-400 rad constitutes ±20% with dose rates of 0.005 to 100 rad/h,

and ±30% with dose rates of 0.0004 to 0.005 rad/h. A record of individual

exposure of cosmonauts to radiation was kept by means of a kit of thermoluminescent dosimeters that they wore at all times, and a set of nuclear

photographic emulsions. The dosimeters can measure radiation doses over

50 mrad with a precision of at least 15%.

Preliminary estimates of radiation dose rates along the path of Soyuz-16

constituted a mean daily level of -10 mrad. For the estimates, we used

data on galactic cosmic radiation during the period of minimal solar activity [1] and the map of distribution of proton and electron flows at different altitudes [2]. We did not determine the effect of solar cosmic rays

on radiation dose rate, since the forecast covering several days showed a

very low level of solar activity and lack of bursts causing radiation

h.i ;urd over the entire period of the mission.

106
The information from the dosimetric instrument installed in the housekeeping

quarters confirmed the estimated data. Throughout the flight, the radiation dose increased uniformly and constituted 58 mrad at landing time.

The doses of radiation recorded by the personal dosimeters presented wide

scatter, because of nonuniformity of the radiation field in the craft, and

they constituted 60-90 mrad.

These tests of the system of monitoring radiation conditions in the craft

bays and levels of cosmonaut irradiation, as well as verification of the

mathods of estimating distribution of cosmic radiation doses along the path

revealed that such a system is very effective in assuring safety of crews

during manned flights in near space over analogous orbits.

BIBLIOGRAPHY

1. Skryabin, N. G., and Sokolov, V. D. in: "Kosmicheskiye luchi" [Cosmic

Rays], Moscow, 1974, p 96.

2. "World Maps of Constant B, L and Flux Contours" (NASA, SP-3054),

Washington, 1970.

107
UDC: 612.115-06:612.766.2].014.47:531.15

BLOOD CLOTTING FUNCTION DURING 12-DAY IMMERSION IN WATER, AND THE

PREVENTIVE ROLE OF REVOLVING ON A CENTRIFUGE

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 79-81

[Article by M. A. Khudyakova and Ye. B. Shul'zhenko, submitted 22 Nov 74]

[Text] There is a sparse literature dealing with hemostasis in the presence

of hypodynamia. Ye. I. Chazov and V. G. Ananchenko [11] failed to demonstrate

changes in 3 out of 4 subjects during 3-day hypodynamia, while one presented

increased anticoagulant and lytic properties of blood. In the case of 20-day

hypodynamia, the same authors found increased fibrinolytic activity of plasma

and higher blood heparin content, as well as lower heparin tolerance of

plasma in the 4 subjects.

According to the report of L. M. Filatova and 0. D. Anashkin [9], an increased thrombogenic potential of blood was observed on the 8th day of

bedrest in horizontal position. Thereafter, a decrease in coagulating

potential of blood was observed in the case of 64-day hypodynamia.

The results of Ye. I. Dorokhova [3], which were obtained with 70-day hypodynamia, revealed that there was a hypocoagulation reaction toward the end

of the first 2 weeks. As the period of hypodynamia increased the hemoph.L.lic reaction also increased in all. subjects.

V. A. Isabayeva and T. A. Ponomareva [4] failed to observe an increase in

thrombogenic properties of blood during 10-day hypodynamia after adaptation

to high altitutde. Longer periods of hypodynamia (24 days) diminished

coagulant properties.

Our objective here was to study the changes in various indices of hemostasis

during 12-day immersion in water and to determine whether it is possible

to use increased gravitation for prevention of "decondition" of the

organism during immersion.

108
Methods

Experiments were conducted with the participation of 14 healthy men; they

involved 12-day immersion in water and combination thereof with period

revolving on a centrifuge. The subjects were immersed to neck level, using

special waterproof fabric. The subjects were revolved on the centrifuge

1-2 times a day starting on the 7th day of immersion; they were supine on

the centrifuge with the head toward the rotation axis. The acceleration

generated by the centrifuge constituted 1-2 G and lasted 90-60 min. The

radius of the centrifuge arm was 7.25 m. The subjects were divided into

two groups: first group (six men) were submitted to "pure" immersion

and the second (eight men), to immersion combined with centrifuge rotation.

We collected blood samples from fasting subjects, using a silicon-coated

needle, from the ulnar vein, and decanted it in silicon-coated glass test

tubes. We used 0.1 M sodium oxalate solution as anticoagulant. During the

test period, plasma was kept in an ice bath. To assess coagulation and anticoagulation capabilities of the organism we determined the following: plasma

recalcification time (PRT) [12), heparin tolerance of plasma (HTP) [17],

plasma thromboplastin time (PTT) [16], plasma thrombin time (TT) [8],

prothrombin complex concentration (PCC) [16], plasma heparin content (PHC)

[8], fibrin content (FC) [6] and plasma fibrinolytic activity (FA) 115].

Blood tests were made twice before immersion and during the period of immersion (2d, 4th, 6th, 8th, 10th and 12th days). The experimental data were

submitted to statistical processing by the Student-Fisher method.

Results and Discussion

The Figure illustrates the changes in coagulation potential of blood of

subjects in the first and second groups. It shows that in the 1st group

on the 2d, 8th, 10th and 12th days, and in the 2d group, on the 2d day of

immersion there was a statistically reliable decrease in PRT (P<0.01),

PTT (P<0.001) and PHC (P<0.01), and increase in HTP (P<0.01), PCC (P<0.01),

FC (P<0.01), and lowered FA (P<0.02). Both groups of subjects presented

equalization of all indices on the 4th and 6th days of immersion.

Total clotting time, as well as HPT, PTT, PCC, TT, PHC, FC, were close to the

initial levels in the 2d group of subjects, on the 8th, 10th and 12th days

of immersion. There was an increase in FA. In the 1st group of subjects,

at these same times, there was an increase in hypercoagulation due to depression of anticoagulation system function (lowering of FA and PHC,

rise of HTP) and an increase in coagulation potential of blood (increase of

PCCand FC).

Analysis of the obtained data is indicative of phasic changes in the system

of hemostasis in man during 12-day immersion. On the 2d day there is hypercoagulation; on the 4th and 6th days the indices level off, i.e., there is

an adaptation phase. Hypercoagulation increases from the 8th day on: there

is significant decline of PHC, slower dissolution of fibrin clot, with increase in HTP, procoagulant concentration and FT. Preventive rotation on

a centrifuge, starting on the 8th day, causes all of the indices to revert

to initial levels.

109
PCC, units FA,min

ITP, s

days

Changes in indices of the blood-clotting system of man during

12-day immersion in water.

X-axis, initial background and days of immersion; y-axis, changes in indices

of hemostasis, in relation to normal. White columns, changes in blood

indices in 2d group of subjects; cross-hatched columns, the same for

the 1st group of subjects

To sum up the findings, it can be concluded that depression of function of

the anticoagulation system of hemostasis is one of the causes of hypercoagulation during immersion in water. This condition is characterized by

a decrease of FA and PHC, and increase of HTP.

According to the data of different authors, the increased concentration of

blood-clotting factors, which elicits an increase in thrombogenic potential

in hypodynamia, may be due to diminished velocity of blood [7], thickening

of blood [14, 18, 19], impaired vascular permeability [1, 2, 5]. In the

presence of these states coagulation factors from formed elements and the

vascular endothelium are discharged into the general blood stream.

We observed a decrease in concentration of procoagulants and increased FA

following periodic rotation on the centrifuge. It is known that hypocoagulation is observed following exposure to prolonged, periodically recurrent

accelerations [10] . Decreased synthesis of procoagulants by the liver is

one of the causes of decreased amount of thrombus-forming proteins in blood

after exposure to accelerations.

The mechanism of increasing FA after accelerations is, according to the data

of Cananau [13] and other authors, related to a change in vascular permeability

and discharge of tissular activator of plasminogen from the vascular endothelium into the general blood stream.

The decrease in blood procoagulants, as well as the increased FA, are beneficial factors and could prevent thrombosis during the period of immersion.

Tims, periodic rotation on the centrifuge was an effective means of preventing disturbances referable to hemostasis of the organism during immersion in

water.

110
BIBLIOGRAPHY

1. Alekseyev, P. P., and Yerokhina, L. S. "Tezisy dokladov 4-go

soveshchaniya po probleme 'Gistogematicheskiye bar'yery"' [Summaries

of Papers Delivered at the 4th Conference on "Histohematic Barriers"],

Moscow, 1969, pp 14-17.

2. Barkagan, Z. S., and Glazunova, G. A. in: "Voprosy nervno-gumoral'noy

regulyatsii protsessa svertyvaniya krovi v usloviyakh normy i patologii"

[Problems of Neurohumoral Regulation of the Blood-Clotting Process Under

Normal and Pathological Conditions], Chita, 1971, pp 25-30.

3. Dorokhova, Ye. I. in: "Problemy kosmicheskoy biologii" [Problems of

Space Biology], Moscow, Vol 13, 1969, pp 109-114.

4. Isabayeya, V. A., and Ponomareva, T. A. KOSMICHESKAYA BIOL. [Space

Biology], No 1, 1973, pp 53-59.

5. Kuznik, B. I.; Rusyayev, V. F.; and Mishchenko, V. P. in: "Stress i

yego patogeneticheskiye mekhanizmy" [Stress and Its Pathogenetic

Mechanisms], Kishinev, 1973, pp 216-218.

6. Rutberg, R. A. LABOR. DELO [Laboratory Record], No 1, 1961, pp 6-7.

7. Simonenko, V. V., and Pekmev, A. P. in: "Eksperimental'nyye i

kliniko-fiziologicheskiye issledovaniya motorno-vistseral'noy

regulyatsii" [Experimental and Clinicophysiological Studies of Motor

and Visceral Regulation], Perm', 1971, pp 92-97.

8. Sirman, E. PROBL. GEMATOL. [Problems of Hematology], No 6, 1957,

pp 38-40.

9. Filatova, L. M., and Anashkin, 0. D. BYULL. EKSPER. BIOL. [Bulletin

of Experimental Biology], No 6, 1968, pp 36-39.

10. Khudyakova, M. A. in: "Materialy nauchnoy konferentsii molodykh

uchenykh In-ta biofiziki" [Proceedings of Scientific Conference of

Young Scientists at the Institute of Biophysics], Leningrad, 1971,

pp 108-109.

11. Chazov, Ye. I., and Ananchenko, V. G. in: "Aviatsionnaya i kosmicheskaya

meditsina" [Aerospace Medicine], Moscow, 1963, pp 476-478.

12. Bergerhof, H., and Roka, L. Z. VITAMIN-, HORMON UND FERMENTSFORSCH.,

Vol 6, 1954, p 25.

13. Cananau, S. A.; Dumitrescu-Papanagi, E.; and Groza, P. REV. ROUM.

PHYSI0L., Vol 10, 1973, pp 441-449.

Ill
14. Johnson PC.; Driscoll, T. B.; and Carpentier, W. R. AEROSPACE MED.,

Vol 42, 1971, pp 875-878. '

15. Kowalski, E.; Kopec, M.; and Niewiarawskl, S. J. CLIN. PATH. Vol 12

1959, pp 215-218. '

16. Quick, A. I. AM. J. MED. SCI., Vol 190, 1940, p 501.

17. Sigg, B. KLIN. WSCHR., Vol 30, 1952, p 205.

18. Torphy, D. E. AEROSPACE MED., Vol 37, 1966, pp 383-387.

19. Vogt, F. B., and Johnson, P. C. Ibid, Vol 38, 1967, pp 21-25.

112
UDC: 612.223.1.017.2

DEFENSE REACTIONS OF THE ORGANISM WHILE BREATHING HIGH CONCENTRATIONS OF

CARBON DIOXIDE

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 81-83

[Article by 0. Yu. Sidorov and Z. K. Sulimo-Samuyllo, submitted 9 Sep 74]

[Text] Man is inevitably exposed to an altered gas environment and, first

of all, high concentrations of C02 when he is in sealed objects.

Various physiological mechanisms can be involved in protecting the organism

from C02; however, their role and extent of participation can alter appreciably, depending on the characteristics of the hypercapnic environment.

In this regard, it is of some practical interest to study the distinctions

of development of defense reactions of the organism, which appear in response to the effects of gradually rising and stationary concentrations of

C02 (to 6%).

Methods

The effects of increasing and stationary concentrations of C02 were studied

in people.

A hypercapnic gas environment was created by adding C02 or C02+02 to inhaled

air followed by delivery of the gas mixture through a mask in the studies

involving increasing concentrations of C02. The concentration of C02 was

increased to 6% in 1, 2 and 5 h, and in the experiments with stationary

concentrations of C02 lasting 1-5 h, they constituted 2, 4 and 6%. The

gas mixture was also delivered to a mask. In the long-term experiments

(10 days), the subjects were kept in a special 12 m

3

chamber, in which the

C02 content was held at the 1-2% level, oxygen content constituted 18-21%,

with 50-80% relative humidity and temperature of 17-22°. Air was regenerated

chemically. Twice a day, compressed air was pumped through the chamber

with concurrent delivery of C02, which maintained the required composition

of the gas environment. We recorded the subjects' pulmonary ventilation,

composition of alveolar air, pulse rate, blood pressure and EKG. In addition, in the long-term experiments, we estimated reserve alkalinity of

blood (RAB), erythrocyte count, hemoglobin, potassium, proteins, amino acids,

as well as pH of blood.

113
Results and Discussion

Removal of CO2 due to mobilization of respiratory system functions is one of

the most important reactions that maintains CO2 in the internal media of

the organism on a stable level. In the experiments with progressively

higher concentrations of CO2, it was established that the presence of a

certain gradient of CO2 increment in inhaled air led to a gradual increase

in pulmonary ventilation and, consequently, better elimination of excessive

CO2 from the organism. It was shown that the high rates of C02 increment,

with which a concentration of 5.5-6% was reached in 1 h, were associated

with more significant increase in pulmonary ventilation. Thus, in the

studies with 1-h increase in CO2 to 6%, pulmonary ventilation constituted

215% at the end of the experiment, in relation to the initial level. With

the same concentration of CO2, but when the increase was made over 2 h,

pulmonary ventilation increased to 174%. CO2 content of alveolar air

constituted 6.5 and 6.2%, respectively, in these experiments (Table 1).

Table 1. Pulmonary ventilation and CO2 content of alveolar air

Nature of experiment

Pulmonary

ventilation, /o

init, level

C02 content of

alveolar air,

% (X±m)

2-h C02 increase to 6%

1-h C02 increase to 6%

174

215

G,2±0,58

6,5±0,G5

Although statistical processing failed to demonstrate reliable differences

in CO2 content of alveolar air in these experiments (P>0.05), the substantial

difference in pulmonary ventilation was definitely indicative of additional

demands and more unfavorable conditions in the case of rapid increase in

CO2 in inhaled air.

In the experiments with 5-h exposure to an environment with 2% CO2, it was

shown that at first the organism prevents rise of PCO2 in alveolar air by

means of hyperventilation. Thereafter, apparently due to gradual decrease

in sensitivity of regulatory mechanisms to CO2, pulmonary ventilation decreases, and this leads to development of a hypercapnic state.

In the experiments lasting for a longer time (up to 10 days), there was

even more marked deficiency of compensatory function of the respiratory

system. This was manifested by lower level of pulmonary ventilation in the

subjects on the last few days of the test, as compared to the first few.

Thus, while ventilation constituted 11.6-12.6 liter/min on the first days,

it dropped to 9.0-9.8 liter/min on the last ones.

114
Table 2. Change in alveolar PC02 and RAB when Inhaled air contains 5.5% CO,

Index

PC02 ..in alveolar air,mm Hg

RAB,vol.%

Initial

background

Criterion

of reliabil.|

Gas environment with

5.-5% C02

M±a

37±1,5

48,8±3,0

t=-2J

P<T0,05

/=3.1

P<"0,01

39+1,2

39,5+3,8

Criterion of

reliability

^---=2,7

P<0,05

t=2,7

P<r0.05

The rate of C02 increment in inhaled air also affected the nature of responses

of the cardiovascular system. In the tests where C02 content was increased

to 5.5-6% in 5 h, the cardiovascular system reacted in the form of slower

heart rate and minor elevation of blood pressure. With increase in rate of

increment (2- and 1-h increase in concentration of C02), instead of inhibition of cardiac activity there was excitation. Concurrently, there was

greater elevation of blood pressure due to an increase in vascular tonus.

A significant increase in vascular tonus, leading to lowering of pulse

pressure and poorer circulation, was observed under the influence of

stationary concentrations of C02. There were also substantial deviations

in functional state of the heart (according to EKG data). In the case of

slow increase in C02 of inhaled air, there were virtually no EKG changes

in the subjects, even when a concentration of 5.5-6% C02 was reached. Brief

exposure to stationary concentrations of C02 (2-4-6%) elicited extreme

lability of P-P, PQ, QT intervals and increase in P and T waves. The

changes in magnitude of the waves occasionally persisted in the recovery

period.

In the experiments with 5-h increment of C02, it was shown that as long as

C02 content of inhaled air did not exceed 3% and pulmonary ventilation was

effective enough the RAB changes were insignificant and within the range of

error of the test. With increase in C02 to 5.5%, there, was an increase in

PC02 in the alveoli and an appreciable decrease of RAB (Table 2).

In several of our experiments, a study of exchange of gases revealed that

with increase in C02 content: of the ambient atmosphere there was gradual

decrease in 02 uptake and C02 output. Oxygen uptake dropped from 264±26 ml

initially to 211+22 ml/min with 3% C02 (P<0.05) and to 176+18 ml/min with

6% C02 (P<0.05). C02 output constituted about 55-60% of the base level. Body

temperature dropped by 0.3°.

Thus, as a result of this study, we established the distinctive features of

development of defense reactions of the organism under the influence of

high concentrations of carbon dioxide; they revealed that the scope, sequence

and extent of involvement of different levels of compensation, as well as

their effectiveness in controlling developing hypercapnia, are related to the

physical parameters of C02 present. It was also shown that, in the case of

exposure to gradually increasing concentrations of C02, the main protective

function would be referable to the most powerful and operational mechanism,

115
the respiratory and cardiovascular systems. At the same time, the role of

other mechanisms (buffer systems, depression of tissular metabolism, etc.)

would be insignificant. The importance of additional mechanisms of compensation increases appreciably with exposure to stationary concentrations of CO2,

particularly in the case of low levels and long exposure. Furthermore, it

was shown that compensatory reactions directed toward improved supply and

utilization of oxygen by the organism play a certain part in the mechanism

of protecting the organism from high concentrations of CO2.

116
UDC: 612.398.194.014.482.4

EFFECT OF GAMMA RADIATION ON INTENSITY OF AMMONIA EXCRETION IN ALBINO RATS

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 83-84

[Article by K. P. Bugar', V. V. Kustov, B. I. Abidin and L. T. Poddubnaya,

submitted 28 Mar 75]

[Text] Exposure of albino rats to 100 R Y

-ra

y

s

°f radioactive 60Co did not

affect intensity of excretion of ammonia, while doses of 300 and 650 R

diminished it.

The literature concerning the effects of ionizing radiation on excretion of

ammonia by irradiated animals is contradictory. According to some authors,

after exposure of albino rats to 400 and 600 R x-rays there was no appreciable

change in ammonia excretion in urine [1, 11]. Other researchers demonstrated

an increased level thereof in urine of experimental animals (albino rats,

dogs) exposed to 600 and 800 R x-rays, respectively [5, 10]. Along with

these data, there is information indicating that exposure of albino rats to

x-rays (700 R) leads, on the contrary, to less excretion of ammonia from the

organism [3, 4]. The contradictory information could be attributed, first

of all, to heterogeneity of experimental material (different species of

animals, dissimilar irradiation conditions). Furthermore, in the works

mentioned above, evaluation was made of the effect of radiation on ammonia

excretion only according to level of excretion thereof in urine, without

consideration of other routes of elimination of this product (gastrointestinal

tract, lungs). At the same time, the data pertaining to overall excretion

of ammonia by experimental animals could be used not only to define the

mechanism of production and elimination thereof in the presence of radiation

lesions, but to design life-support systems on biosatellites and formation

of an artificial atmosphere. By the 18th-20th day of a mission, the ammonia

level in the air of spacecraft could reach hygienically significant amounts

[6].

Methods

Experiments were conducted on 12 male albino rats with initial weight of

180-220 g. The animals were divided into four groups, so that there would

be the same number of animals of the same weight in each group. The

117
animals in the 1st, 2d and 3d groups were placed in plastic boxes and exposed

to Co Y-rays (dose rate, 27 R/min) in doses of 100, 300 and 650 R, respectively. The fourth group of animals (control) was not exposed to ionizing

radiation. Some of the experimental and control rats were sacrificed on the

1st, 3d and 10th postradiation days for subsequent assay of ammonia content

of blood by the method of Miller and Rice [12].

We determined elimination of ammonia by irradiated animals according to the

difference between total amount of this product in condensate and air of the

chamber after experimental and control rats had spent 24 h in it (each

group consisted of 10 animals and the tests were repeated 3-4 times). Oxygen

and carbon dioxide content of the artificial atmosphere in the hermetically

sealed chamber, 93 liters in size, was kept at 20-24 and 0.2-1%, respectively.

A constant air temperature (20°) and relative humidity (not exceeding 70%)

were maintained by means of a system of thermoregulation and collection of

condensate of atmospheric moisture. Ammonia content in the air of the

chamber and condensate was determined by the method of M. I. Poletayev and

N. A. Andreyeva [7].

mg/kg/clay

WO R 300 R 650 R

Effect of Y~radiation on blood ammonia content and intensity of

excretion thereof.

Striped band, physiological "norm" of index; K, initial level thereof.

The numbers in the columns refer to day of observation on top and number

of animals on the bottom.

118
Results and Discussion

The Figure illustrates the results of our experiments. Exposure of the

animals to 60Co y-rays in a dosage of 100 R (1st group) did not have an

appreciable effect on ammonia level in blood and total elimination thereof.

With increase in radiation dose to 400 R (2d group) and 650 R (3d group),

blood ammonia content diminished in experimental animals. However, a

substantial difference between base value of this index, as well as the

physiological ammonia "norm" in rat blood and amount of this product in the

blood of experimental animals was recorded only on the 10th postradiation

day. The intensity of excretion of ammonia also diminished: on the 1st and

3d postradiation days, with exposure to doses of 300 and 650 R, daily excretion of ammonia per kg body weight differed appreciably from the initial

level of this index in experimental rats, and it was considerably lower than

the physiological range in control animals. By the 10th experimental day,

the intensity of excretion of ammonia in irradiated rats virtually reached

the lower range of the physiological norm.

Thus, the results of our experiments revealed that y-radiation has no effect

on excretion of ammonia by irradiated animals with a dosage of 100 R,

whereas in doses of 300 R and 650 R it lowers excretion thereof. The lower

intensity of elimination of this product after exposure to 300 and 650 R

ionizing radiation could be due, to some extent, to impaired functional

state of the gastrointestinal tract, which is the main supplier of ammonia

in the organism [2] and decreased excretion thereof in urine due to inhibition of the process of deamination of amino acids [8] and biogenous amines

[1], which is one of the sources of ammonia formation in the organism.

Evidently there are also other mechanisms involved in this phenomenon, and

they require special investigation.

BIBLIOGRAPHY

1. Akopyan, Zh. I.; Gorkin, V. Z.; Kudryashov, Yu. B.; et al.

RADIOBIOLOGIYA [Radiobiology], Vol 10, 1970, pp 826-831.

2. Kozlov, N. ti. "Ammonia—Its Metabolism and Role in Pathology," Moscow,

1971.

3. Kolosova, T. S.; Tiunov, L. A.; Kustov, V. V.; et al. IZV. AN SSSR.

SER. BIOL. [News of the USSR Academy of Sciences. Biology Series], No 4,

1970, pp 613-617.

4. Kustov, V. V., and Tiunov, L. A. "Problemy kosmicheskoy biologii"

[Problems of Space Biology], Moscow, Vol 11, 1969, pp 88-98.

5. Perepelkin, S. R. "The Protective Effect of Food and Vitamins in the

Presence of Radiation Lesion to the Organism," Moscow, 1965.

119
6. Pliskovskaya, G. N.; Germanova, A. L.; Ivanov, N. G.; et al.

KOSMICHESKAYA BIOL. [Space Biology], No 2, 1975, pp 27-32.

7. Poletayev, M. I., and Andreyeva, N. A. GIG. I SAN. [Hygiene and

Sanitation], No 6, 1959, p 73.

8. Protasova, T. N. in: "Patologicheskaya fiziologiya ostroy luchevoy

bolezni" [Pathological Physiology of Acute Radiation Sickness], Moscow,

1958, pp 162-172.

9. Fedorova, T. A.; Tereshchenko, 0. Ya.; and Mazurik, V. K. "Nukleinovyye

kisloty i belki v organizme pri luchevom porazhenii" [Nucleic Acids and

Proteins of the Organism in the Presence of Radiation Lesion], Moscow.

1972.

10. Kolousek, F.; Jiracek, V.; et al. NEOPLASMA (Bratislava), Vol 12. 1965

p 565.

11. Lamerton, L.; Elson, L.; and Christensen, W. BRIT. J. RADIOL., Vol 26

1953, p 510.

12. Miller, I. E., and Rice, F. D. AM. J. CLIN. PATH., Vol 39, 1963,

pp 97-103.

\

j

; i2o

\

!

(

1

i
ÜDC: 629.78;612.886

OTOLITH SYSTEM FUNCTION IN COSMONAUTS FOLLOWING SPACE MISSIONS

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 85-86

[Article by F. A. Solodovnik, submitted 7 Jul 75]

[Text] The experience of flying in space indicates that some cosmonauts

present symptoms of motion sickness and illusions of spatial position on

the 1st day of missions. It is believed that such disorders are the result

of distinctive stimulation, in an environment that is unusual to man, of

receptors of physiological systems that control spatial position and mainly

the vestibular analyzer [1, 2, 5, 6].

Perhaps prolonged weightlessness leads to functional reorganization of

the otholithic system, and after returning to earth the cosmonauts have to

undergo reverse adaptation to gravitation conditions.

The objective of this work was to investigate the functions of the otolith

system of cosmonauts before and after a space mission.

Methods

These studies were pursued using a swing suspended on four rods, with revolving

scat [3]. The back and seat of the swing were lined with porolon. The

cosmonaut was strapped tightly in the swing seat. His head was tiled 30°

forward, the eyes were shut and light-proof glasses were worn. The magnitude of deviation of the swing from the vertical line was recorded on a

special scale. In order to disorient the cosmonaut, he was rotated in

the swing chair prior to the study, at the rate of 15°/s. After 2-3 turns,

the seat was stopped in one of six positions: 0 and 180° by swinging forward

and backward; 90 and 270° positions to the left and right, and 225 and 315°

at an angle of 45°. To rule out the possibility of orientation in relation

to the direction of swing movement, the studies involved stopping the

swing in the following positions: 90, 225, 0, 315, 270 and 180°.

After: rotating the cosmonaut in the swing seat, 20 s after disappearance of

the illusion of reverse rotation, we began to push the swing, gradually

increasing amplitude to 0.5 cm. Two complete swinging movements were made

(two periods) at this amplitude; the amplitude was then increased by 0.5 cm

and another two swings were performed, etc. With increase in amplitude, the

121
cosmonaut fixed the time of appearance of the sensation of swinging and,

if he was able, indicated the direction of movement of the swing with the

palm of his hand. But if he could not determine the direction of swinging

at the start, i.e., at a low amplitude, we continued to increase the amplitude of swinging until he was able to confidently and correctly determine

his position in relation to the direction of movement.

Maximum acceleration in the horizontal plane was calculated using the

following formula:

A

a -jg

where a is linear acceleration, A is amplitude of swinging, I is the length

of the swing rods and g is acceleration of free-falling body.

We tested functions of the otolith system of the cosmonauts before a mission

and 3 days after landing. A total of 10 cosmonauts participated in our

studies; they had performed space missions lasting 3 to 28 days.

Results and Discussion

All of the cosmonauts perceived rather accurately the start of swinging

under the influence of low linear accelerations, and they determined the

direction of movement of the swing mainly after subsequent increases in

swinging amplitude. A comparison of the results of testing threshold

levels of linear accelerations before and after space flights failed to

demonstrate appreciable differences (see Table). Nor were there any reliable

changes in threshold levels of perception of the vector of linear acceleration, regardless of the cosmonaut's position in relation to direction of

movement of the swing. The minor drop of all mean indices after a space

flight was perhaps related to a somewhat higher emotional state of the

cosmonauts at this time.

Threshold levels of perception of linear acceleration by cosmonauts, cm/s2

(M±m)

Threshold of Threshold of perception of direction of linear

perception of acceleration. Cosmonaut's position in relaTirae of linear tion to direction of movement of swing

examination acceleration head in direct.of movement 90° angle 45° angle

Before flight 4.0±0.24 10.7+1.08 11.8±0.56 17.6±1 71

After flight 3.2+0.43 7.0±1.03 8.5±1.95 17.2il.45

When swinging, mainly periodically changing direction and magnitude of

linear acceleration affect receptor systems of the organism, as well as

minimal stimuli of no practical significance: change in force of gravity

and centripetal acceleration. It is known that the receptors of the otolith

system are stimulated with tangential displacement of otoliths [7, 8].

122
Swinging at a low amplitude stimulates primarily the otolithic system in man.

This has been convincingly demonstrated in the experiments of Walsh [9].

The obtained results of studies of threshold levels of perception of linear

acceleration and vector thereof do not differ appreciably from the results

of experiments involving people of other than flight specialties [4].

A comparison of the results obtained on cosmonauts who had been on space

missions varying in duration also failed to demonstrate differences in

capacity to perceive linear acceleration.

Thus, no appreciable deviations of otolith system functions were demonstrated

in cosmonauts 3 days after they had been on space missions lasting 3 to 28 days.

The obtained data are consistent with clinical observations, which failed to

demonstrate any deviations in vestibular function. Perhaps, with up to 28 days

of weightlessness the otolithic system remains unchanged, or else the

deviations that do appear in its function are brief and soon disappear upon

returning to earth's gravitation. This question requires further investigation.

BIBLIOGRAPHY

1. Yemel'yanov, M. D. in: "Fiziologiya vestibulyarnogo analizatora"

[Physiology of the Vestibular Analyzer], Moscow, 1968, pp 5-14.

2. Komendantov, G. L., and Kopanev, V. I. in: "Nevesomost'" [Weightlessness], Moscow, 1974, pp 74-83.

3. Markaryan, S. S.; Sidel'nikov, I. A.; Popov, N. I.; et al.

[Military Medical Journal], No 11, 1971, pp 81-83.

VOYEN.-MED.ZH.

4. Solodovnik, F. A., and Alekseyev, V. N. IZV. AN SSSR. SER. BIOL. [News

of the USSR Academy of Sciences. Biology Series], No 4, 1974, pp 499-505.

5. Yuganov, Ye. M., and Goshkov, A. I. in: "Problemy kosmicheskoy

biologii" [Problems of Space Biology], Moscow, Vol 3, 1964, pp 167-176.

6. Grayliel, A. AEROSPACE MED., Vol 40, 1969, pp 351-367.

7. Miller, E. F. ACTA OTOLARYNG. (Stockholm), Vol 54, 1962, pp 479-501.

8. DeVries, H. Ibid, Vol 38, 1950, pp 262-273.

9. Walsh, E. G. J. PHYSIOL. (London), Vol 155, 1961, pp 506-513.

123
UDC: 616.8-009.832-057-092:612.014.47]:613.693

SUDDEN LOSS OF CONSCIOUSNESS IN PILOTS WITH LOW INTRAOCULAR PRF^imr nuPTwr EXPOSURE TO G FORCES miKAUCULAR PRESSURE DURING

"TTmTlTlt^f BI0L0GIYA '

AVIAK0SHI

« A MEDITSXNA In Russian

[Article by Yu. Domashuk and M. Voytkovyak, submitted 14 Dec 74]

hyperventilation, G forces and others [2 3 51 A Phenomenon: hypoxia,

G forces are rather significant! ' '

]* ^^ th6m' "head-pelvis"

It should be noted that loss of consciousness in the presence of C fnrrp,

is not usually sudden, and it is virtually always preceded by visualdis

turbances m the form of a gray or black covering [1, 4] Y*~

During linear increment of G forces at thp ratP of n i •. /

»eat of peripheral vision should occur ^f«^^^rT^

loss of consciousness. However mass „rp^inn f •.

; prior to

(determination of ra„8e or «d»'»"^^^''^^'^ li^r'SS-

::rb fdSs urbae„Lrr" ribJrtr"ssi:„hen £• of —"—s"" ~<^-

in order to determine the caused Äpbeuomenon" "^ - ^"«^

Methods

^.U^K- T f°T °! Pil0tS; the first Sroup consisted of seven people

cursors iTatesHfrl SUdde'\

1

°

ss °£

consciousness without visS/presecr

:„dS(cLrr:ietgrL ^^0 ^}^"^ th * """'f^' ^

was determined on the basis of visual d'isord^s" ' f thTsubJ ctfhaT"

undergone a comprehensive clinical and laboratory „ork-un D » •

»eats, and the results faiied to demonstrate any ^."Jo»" ".^.^"-

cxp""urert„ C

1

"forc«larT

P

r

eSS,,r

, "'^ °

Schl°«"> tonometer immediately after

£s«;-- c:^o„f^r"^rp^t-^rLd^o„"r:rutJk2r:„r:

rate and arterial pressure both before and after the experiment

124
We were particularly concerned with comparative determination of intraocular

pressure in both groups of pilots, as well as the effects of G forces on

this index.

Results and Discussion

The range of endurance of G forces constituted 4.5 to 7.4 units (mean of

6.29±0.962 units) in the first group of pilots, and there was no statistically

reliable difference from the second group (6.50±0.915 units), in which maximum

endurance was evaluated on the basis of visual disturbances. Moreover,

circulatory indices (pulse and arterial pressure) were similar in both groups

of subjects.

However, intraocular pressure, measured after the experiment, was below the

physiological norm in the first group, constituting 11.70Ü.44 mm Hg, which

was reliably different from the same index in the second group

(16.27±3.01 mm Hg).

The results of studying the effects of maximum tolerable G forces on intraocular pressure revealed a statistically reliable (P<0.01) drop of intraocular pressure (from 18.79±2.90 in the background to 16.27±3.01).

Thus, as indicated by the data obtained, low intraocular pressure during

exposure to G forces may be the cause, [sic]

On the basis of the results of our investigation and in view of the fact that

we failed to observe instances of sudden loss of consciousness in individuals

with normal intraocular pressure, it can be concluded that one should measure

intraocular pressure in all pilots exposed to G forces, for preventive

purposes.

BIBLIOGRAPHY

1. Adler, F. H. "Physiology of the Eye. Clinical Application," St. Louis,

1970.

2. Conn, J. W., and Seltzer, H. S. AM. J. MED., Vol 19, 1955, p 460.

3. Evrard, E., et al. (editors), "Medical Aspects of Flight of Safety.

(The Unexplained Aircraft Accident)," London, 1959, p 102.

4. Gillies, J. A. in: "A Textbook of Aviation Physiology," Oxford, 1965,

p 562.

5. Powel, J. T. AVIAT. MED., Vol 27, 1956, p 301.

125
BOOK REVIEWS

UDC: 612.886(049.3)

NEW BOOK DEALS WITH PHYSIOLOGICAL FUNCTIONS OF THE VESTIBULAR SYSTEM

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 pp 87-88

[Review by M. D. Yemel'yanov of the book "Fiziologicheskiye Funktsii

Vestibulyarnoy Sistemy" by A. Ye. Kurashvili and V. I. Babiyak, Izdatel'stvo

Meditsina, Leningrad Department, 1975, 279 pages]

[Text] The authors' objective was to summarize the information in the

literature and report the results of their own clinicophysiological research

on pressing problems of physiology of the vestibular analyzer.

The book consists of an introduction, seven chapters, conclusion and

bibliography.

Chapter 1 describes the structure of the peripheral part of the vestibular

analyzer (receptors) and vestibular nuclei. Their efferent (outgoing) and

afferent (incoming) relations are traced to some elements of the central

nervous system, and their functional characteristics are given.

The chapter is, to some extent, a repetition of material summarized in the

monographs of Sentagotay (1950-1952), Brodal et al. (1966), A. N. Razumeyev

and A. A. Shipov (1969) and Ya. A. Vinnikov (1971). However, it is apparently

necessary, since it offers an integral idea about the objectives of the book.

The authors could be reproached for failing to provide a clearcut structural

and functional definition of the very concept of vestibular analyzer.

Chapter 2 discusses the concept of an adequate vestibular stimulus in the

form of mechanical forces. Acceleration and velocity cannot be stimuli on

their own, i.e., carriers of energy. It would seem that such an interpretation precludes use of the term "acceleration" as a stimulus of vestibular

receptors. Yet many researchers disregard this fine point in their work.

The mechanisms of excitation in the semicircular canals and otolith system

are described rather well, with mathematical computations covering the

intensity and duration of a stimulus, as well as its vector.

126
Cupulometry is submitted to critical discussion. Load tests and continuous

stimulation of the vestibular system using measured, variable-polarity accelerations are considered to be more promising methods for evaluating vestibular

function.

Unfortunately, not enough attention is given to a discussion of inadequate

methods of vestibular stimulation.

Chapters 3 and 6 cover the general pathogenetic mechanisms of the processes

in question. Perhaps it would have been more expedient to do this in one

chapter. There is graphic demonstration of the fact that it is important

to hold spatial coordinates that are fixed in relation to the gravitational

vertical in the field of vision to retain equilibrium of the body. In this

regard, a section on vestibular nystagmus occupies a significant place.

Chapter 6 deals with the important question of interaction of vestibular and

visual analyzers. There is discussion of vestibular influences on fixing

function of the eyes and some distinctions of tracking movements. Modulation

of efferent fixation function is, in the authors' opinion, the result of

central convergence of vestibular and optokinetic afferents (reticular formation, thalamus, cerebral cortex) and formation of a modified spatial image

on the basis thereof. For this reason,- a "jump" or turn of the eyes in

a specified direction is very precise (even in the absence of a visible

target).

Chapter 4 is of interest to physiologists. There is valid substantiation of

the borderline between normal vestibulovegetative and pathological reactions.

The former supply the energy balance of the muscle system in maintaining a

pose, equilibrium and spatial orientation, i.e., in the presence of functional

vestibulosomatic reflexes. In this sense, the capacity to activate adaptational and trophic function of the autonomic nervous system is attributed to

the vestibular analyzer. The authors' own experiments enabled them to expound the hypothesis that there is afferent representation of the vestibular

analyzer in elements of the limbic system.

Efforts to find features in common in motion sickness and Selye's syndrome

lead to some contradictions. The fact that some individuals are affected by

motion sickness and others are not, discrete forms of these processes, lack

of pattern in development of vegetative disorders and the classical triad

of Selye in virtually all cases are not consistent with the Selye syndrome.

The authors discuss the hypothalamus as the main source of the first and

second phases (in their classification) of the adaptation reaction in motion

[sea] sickness and transformation of a nervous signal into a humoral one.

The statement that an angioneurotic component is the initial pathogenetic

mechanism of the entire set of symptoms of sea sickness (p 160) is debatable.

At the same time, in our opinion, studies directed toward determination of

the functional state of carotid glomeruli and their role in regulating

127
circulation in the presence of vestibular stimulation are not without interest,

Data have been obtained on a different level of regulation in the presence

of specific vestibular stimuli and the effects of stimulation of the carotid

sinus on nystagmus.

Chapter 5 deals with little-studied aspects of vestibulology. The authors

develop the teaching on the essence of excitation in nerve centers. It is

stressed that processes arising in the vestibular system with simulation of

successive reactions do not end with their primary manifestation, but continue in the form of phasic reactions. The number of phases and their duration depend on the force of the vestibular stimulus.

In Chapter 7, the authors raise very validly the question of involvement of

the set of analyzers in evaluation of spatial position, on the one hand; they

attribute appropriate significance to psychophysiolögical aspects. On the

other hand, they exaggerate somewhat the role of the vestibular system.

We tend to consider interaction between the visual and vestibular analyzers

from the standpoint of more refined correlations occurring as a result of

the effects of various stimuli, both on the level of vestibulooculomotor

reactions and cortical sensory relations.

In the conclusion, concrete routes of future research are delineated with

reference to functions of the vestibular system, of which the following are

the most important in our opinion: the problem of analyzer interaction on

different levels of nerve structures, mechanisms of sea sickness, spatial

illusions and control of vestibular reflexes.

On the whole, the book merits a high rating.

This monograph will be of definite interest and usefulness to a wide circle

of readers: otorhinolaryngologists, physiologists, mainly in the field of

space physiology, psychologists, etc.

128
UDC: 613.693(092)Volynkin

BIOGRAPHY OF YUVENALIY MIKHAYLOVICH VOLYNKIN (ON HIS 70TH BIRTHDAY)

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

JNO 3, 19/7 p 89

[Article by the editorial board]

[Text] There are people whose life has many directions and wide scopetheir endeavors are particularly remarkable, and their personal charm '

compels all those around them to treat them with the deepest respect

Yuvenaliy Mikhaylovich Volynkin, a brilliant specialist, excellent organizer,

ardent patriot and remarkable human being, is unquestionably such a person.

In'l932V°

lynkin gradUated fr°m the Military Medical Academy imeni S. M. Kirov

Yuvenaliy Mikhaylovich first came into aviation medicine as a medical laboratory technxcian, then as head of the psychophysiological laboratory.

In 1936, Yuvenaliy Mikhaylovich was promoted to the post of senior inspector

for medical support of high-altitude and high-speed flights, where his

great organizational talents were manifested.

In 1939, Yu. M. Volynkin participated in the Soviet-Finnish War, as head of

an evacuation hospital. He was an active participant in creating the

hospital base of the Eighth Army. This was the birth of a great organizer.

The Great Patriotic War found Yuvenaliy Mikhaylovich as one of the heads

of the Main Military Medical Administration of the Soviet Army. Yuvenaliy

Mikhaylovich developed and created new and original structures of the

medical service of the combat units of the USSR Armed Forces. He was

directly involved in implementing formation of a network of front-line

hospital bases and deployment of a network of educational medical institutions

Training of qualified medical personnel for the Armed Forces was implemented

under the direct supervision of Yu. M. Volynkin. In 1951, Yuvenaliy

Mikhaylovich was assigned deputy head of the Military Medical Academy imeni

b. M. Kirov, where he implemented major organizational and methodological

measures directed toward reorganizing the training of military physicians,

7i, ? ^,e

c

cons:Lderat±on of the knowhow gained in the Great Patriotic War of

1"Al—LyHj.

129
t,r'J'^M.%l

From 1954 to 1968, Yu. M. Volynkin implemented a number of brilliant organizational

measures; he displayed a profoundly

creative approach to planning and performance of difficult scientific work in the

field of aviation and space research.

During this period, screening and training

of the first cosmonauts were implemented

under his immediate supervision; the

principles of medical and medicq,technical

support of space flights in our country

were substantiated at this time.

In 1969, Yuvenaliy Mikhaylovich was transferred to the reserves with the rank of

Lt General. Since then and to the present

time, as assistant to the director of the

Institute of Biomedical Problems, USSR

Ministry of Health, Yu. M. Volynkin is

successfully solving all of the organizational-methodological and planning problems

pertaining to scientific research at this

institute.

We are particularly proud to have had the opportunity to be with this

charming man, wise organizer and expert with enormous experience. The government has shown its appreciation to Yuvenaliy Mikhaylovich Volynkin for his

brilliant handling of large and responsible State assignments, his exceptional industriousness and high degree of versatile qualifications; he is

the recipient of two Orders of Lenin, orders of the Red Banner and Red

Banner of Labor, three orders of the Red Star and many medals.

Along with his numerous disciples and comrades in arms, we sincerely wish

Yuvenaliy Mikhaylovich Volynkin good health and new creative achievements

for the good of our Great Homeland.

130
UDC: 629.78(092)Korolev

OBITUARY OF SERGEY PAVLOVICH KOROLEV (ON HIS 70TH BIRTHDAY)

Moscow KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA in Russian

No 3, 1977 p 90

[Article by the editorial board]

[Text] An era of significant achievements is linked with the name of

Academician Sergey Pavlovich Korolev, oustanding Soviet scientist, designer

of space rocket systems, twice named Hero of Socialist Labor and one of the

founders of practical cosmonautics: development of high-power space rocket

systems, the first flight in space of Yu. A. Gagarin, extravehicular

activity of man in space, photography of the moon, creation of interplanetary

stations to the moon, Venus and Mars. In each of these achievements,

there was wide use of the scientific and technical ideas of S. P. Korolev;

to each of them he made an appreciable contribution, thanks to his outstanding organizational skills and talents of a great scientist, who was able

to provide, for a number of years, the directions for development of Soviet

cosmonautics and to guide the work of many scientific research and designing

teams to perform their assigned tasks.

S. P. Korolev always paid much attention to problems of biomedical support

of manned space missions; he constantly collaborated in the creation and

development of a new branch of science, space biology and medicine.

Even in the early days of his scientific activities, in 1934, he wrote in

his work "Rocket Flight Into the Stratosphere": "Let us discuss the characteristics of jet craft equipped with engines using liquid fuel. First,

there is the crew.... Second, life support.

This will include all the devices, instruments and equipment to maintain

living conditions for the crew and efficiency at high altitudes." And in

his subsequent work, Sergey Pavlovich repeatedly returned to this problem,

devoting his attention mainly to development and safe and reliable life

support devices in space.

S. P. Korolov attributed special importance to question of screening and

training cosmonauts. He was a frequent visitor at Zvezdnyy town; he

constantly observed the studies of future cosmonauts; he delivered lectures

131
to them himself and was a strict interrogator at their examinations.

Sergey Pavlovich collaborated successfully and maintained personal contact

with outstanding scientists and organizers of Soviet medicine: A. I

Burnazyan V A. Engel'gardt, N. M. Sisakyan, V. V. Parin, A. V. Lebedinskiy,

Yu. M. Volynkin, V. I. Yazdovskiy and other figures in Soviet science.

Many of the scientific ideas and technical proposals of S. P. Korolev were

implemented after his death. The long-term orbital stations, spacecraft

for exploration of Venus, systems of radio communication in space and

specialized satellites of significance to the national economy are the

next landmarks of Soviet cosmonautics, in each of which there is a particle

of selfless labor and talent of Sergey Pavlovich Korolev.

S. P. Korolev wrote: "I cannot help wanting to exclaim how much has been

done and accomplished, and at the same time cannot fail to state how little

has been accomplished, how much more there is still to do."

COPYRIGHT: KOSMICHESKAYA BIOLOGIYA I AVIAKOSMICHESKAYA MEDITSINA, 1977

10,657

CSO: 1849 END

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