HEMODYNAMIC CHANGES IN THE SMrlLL VESSELS IN MAN AS
     ANALYZED BY DIGITAL PLETHYSMOGRAPHY I
                                                      A
   ROBERT L.LJOHNSON*, M.D., EDWARD D.,FREIS, M.D. AND
           HAROLD W. SCHKAPER, MB.
                 G
Although fairly adequate methods are available for the study of the hemo-
dynamics of the arterial circulation .and overall blood flow to various areas,
little is known of the dynamic.changes which occur in the small vessels in man.
Aside from the observations of "Thomas Lewis (1) on the terminal circulation
in the human skin, and measurements of static capillary pressure by Landis
(2), further explorations have been hampered by the lack of suitable methods
of st.udy. On the other hand much has been learned about, the minut.e vessels
from investigations in living animals and from anatomic specimens.
Anatomically the capillary bed begins with the metarterioles jvhich arise
as branches or prolongations of the terminal arterioles. The metarterioles form
the initial portions of the so-called preferential or t,horoughfare channels de-
scribed by Chambers and Zweifach (3) which, after a relatively long course,
join similar channels and terminate in the venules. Numerous sphincteric
muscular buds, the precapillary sphincters (4), which originate at, various
interyals along the early portion of the thoroughfare rhannels, make up the
proximal ends of the true capillaries. These small endothelial vessels in turn
empty into the distal segments of the same or other thoroughfare channels.
In addition to these components of the small vessel unit there occasionally
are relatively large short, vessels, the arteriovenous anastomoses, &ieh arise
from metarterioles or arterioles and empty directly into venules.
Changes in the diameter of t,he proximal portions of the thoroughfare chan-
nels permit flow through these vessels to be independent of pressure and flow
conditions in the systemic circulation. Further, the pulsatile quality of the
blood flow in the larger arterial vessels is replaced by a relatively continuous
flow through the thoroughfare channels. Alternate opening and closing of the
precapillary sphincters produces an intermittent type of flow through the capil-
laries. These alternating periods of spontaneous const,riction and relasation of
the metarterioles and of the precapillary sphincters, a process known as vase-
motion (5), allows adjustment of the circulation through the capillary unit as
necessary to provide for the metabolic requirements of the tissue at any moment
and in the skin to serve as radiators of body heat. The arteriovenous anastomoses
(6) are usually closed during normal conditions but open under special circum-
stances of blood flow.

From the Cardiovascular Research Laboratory, Georgetown University Hospital,
The Department of Medicine, Georgetown University School of Medicine and the Veterans
Administration Hospital, Washington, D, C.
This invest.igation was supported in part by research grants from the Sational Heart,
Institute, U. S. Public Health Service, The Squibb Institute for Medical Research, Sew
Brunswick, New Jersey and Irwin Seisler and Company, Decatur, Illinois.
*Captain, MC, U.S.A.F.
                           412


HEMODYNAMIC CHANGES              413

During the course of studies on the effects of drugs on the digital plethysmo-
gram certain consistent patterns of blood flow, pulse volume and digital volume
\vere observed depending upon the agent being used. The analysis of these
patterns suggested a relationship to hemodynamic changes in the small cutaneous
vessels. The purpose of t,his report is to present an interpretation of these ple-
thysmographic patterns in terms of changes in the small vessels and to correlate
this data with direct observations of the vasculature of the bulbar conjunctiva.

METHODS

Blood flow, digital volume, and pulse volume were measured in the large
toe of young normal subjects using a Burch-Winsor portable plethysmograph
(7). Digital blood flow was measured by the venous occlusion method (8) using
a congesting cuff placed at the base of the digit or at the ankle and inflated to
15 to 20 mm. Hg below the diastolic blood pressure. When technically possible,
occlusion at the base of the digit was carried out. However, with high rates of
blood flow occlusion at the base of the digit produced such a rapid increase in
digit'al volume that accurate measurements of flow were not possible. Under
these conditions it was necessary to use the occluding cuff at the ankle and
t,he values so obtained were multiplied by 3 as suggested by Goetz (9). Although
t,he ratio between digital and ankle occlusion appeared to vary somewhat in
different individuals and with varying rates of blood flow in the same individuals,
a factor of 3 appeared t,o be sufficiently accurate for purposes of comparison.

Large changes in digital volume could not be accommodated in the plethysmo-
graph without adjusting the position of the volume-recording aluminum capsule
upon which the bowstring assembly was mounted. Since this adjustment pro-
duced a change in the sensitivity of the .recorder a slight modification of the
machine was necessary in order to measure volume changes without altering
any of t'he adjustment mechanisms Accordingly a horizontally placed pipette
with 0.01 cc graduations and containing a drop of mercury was incorporated
into the pneumatic system. By manipulation of the plunger of a tuberculin
syringe attached permanently to the distal end of the pipette the mercury
column could be moved a measurable distance to accommodate for changes
in the volume of the digit, thus affording a quantitative determination of digital
volume at any time.

The direct recording of arterial pressure (10) and the estimation of foot
blood flow and skin temperature were determined according to methods de-
scribed elsewhere (11). Determinations were made in a constant environmental
temperature of 68 to 70oF. Control values were obtained only after the subject
had been at rest in the supine position for at least 45 minutes. The foot of the
bed was elevated on 2-inch blocks to minimize the effects of postural hypoten-
sion. Blood flow was determined at frequent intervals and each value represented
the average of two or more closely spaced observations.

Direct observation of the bulbar conjunctiva was made using a Bausch and
Lomb binocular dissecting microscope with a magnification of 30 X. However,
it was not possible to obtain sufficient illumination to take photographs through


414            JOHNSON, FREIS AND SCHNAPER

the microscope. Hence, these were taken directly using a Leica 35 mm. camera
with a 180 mm. extension tube and a 9 cm. Elmar Leitz lens. Illumination was
furnished by a Bardwell-McAllister Baby Keg-Lite with a 750 watt lamp
equipped with a Foco-spot. Exposures were made on Panatomic film with a
lens opening of f. 4 at l/100 second. The final magnification after further en-
largement of the films was 15 X.

RESULTS

Digitat Blood Flow, Digit& Put$e Volume, and F.TVXOTU~ Pulse Pressure after C6
        as Compared to Lumbar Epidural BlocS
In normal subjects who were given 50 to 100 mg of CO intravenously and on
another day lumbar epidural block, the increases in toe blood flow mere essen-

TABLE I

Effecfs oj hezamelhonium, lumbar epidural block and priscoline on digital volume, digital
             pulse volume, and digital blood $0~:

      PBWBDUPS        NUYBEP   Average
        oPC~s=S iapl&m Ag;F   ! Average ' Average ' Avw&af;
                                      Time to 1 Maximum
                                  Reach  &.zzm '         ieach
                           cc per   Maximum   cc per    Reach  /  cc per 10
                                      hlaximum /  cc per   Maximum
                           10 cc    Minutes   10 CC   Minutes I Minute   Minutes
                   -pF-IT-p
          Kw                                  1
Hexamet~onium
(Intravenously). .   IO     1.1     15    0.25 15     4.7     35
Lumbar Epidural Block.    7     1.1     25   1 I
                             0.36 20 , 4.9     40
Priscoline (Intraarteri-
ally)...................    3     0.8     7    0.12     5 I /
                                                1.1     15

* Average values during control period were for pulse volume 0.001 cc. per 10 cc. of
digit and for blood flow 0.14 cc. per 10 cc. of digit per minute.

tially similar either after C6 or after lumbar block, the maximum flows in each
instance averaging 5 cc per 10 cc of digit per minute (Table I, Fig. 1). The
blood flow of the entire foot as determined in the opposite extremity also indi-
cated no significant difference between the increase in flow after C6 and after
lumbar block (11). H owever, digital pulse volume always was 30 to 50 per
cent greater after lumbar block than following C6 (Table I, Fig. 1).

Since it appeared possible that the relatively smaller pulse volume after C6
compared to lumbar block might be due to the effect of this agent on arterial
pulse pressure, the plethysmographic studies were repeated with simultaneous
measurement of fenioral arterial pressure in the limb under study using a hypo-
dermic manometer. After C6 there was a significant fall of arterial pressure,
especially of the systolic pressure, and an increase in heart rate producing a
rather marked decrease in pulse pressure {Fig. 2). Slight decreases of both
systolic and diastolic pressures without change in heart rate were observed
in the femoral artery after lumbar block but this did not produce any significant
changes in pulse pressure.


L

DIGITAL PULSE VOLUME - CC/IO CC

;I j!&\;~~~~
     DIGITAL BLOOD FLOW - CC/!0 CC./MIN.

I     cl C6       I EPIDURAL BLOCK

6                   -
5
4

CONTR(K'   lb 2b   30 40   $0 d0 70

TIME - MINUTES

FIG. 1. Chart comparing the effects of the intravenous injection 50
the lumbar epidural injection of 600 mg of Metycaine on digital pulse
How in subject B. B., a normal male, age 29 years.

mg of C6 ion and
volume and blood

L

ARTERI

120

80

40

0

FIG. 2. Cuttings from the tracings of femoral arterial pressure and digital pulse volume
before and after the intravenous injection of C6 ion in subject P.S., a normal male, age 25
years. The ~~~ethysmographic tracing in the control is at a slow paper speed and after C6 at
a rapid speed. During the-period of maximum increase in pulse volume there is consider-
able decrease in arterial pressure, especially pulse pressure.
                           415


416             JOHNSON, FREIS AND SCHNAPER

Di$erential Changes in Digital Volume, Pulse T'olume and Blood Flow after CS
OT Lumbar Block in Relation to Time. Vessels of the B&bar Conjunctiva
Following C6 there was a rapid increase in both digital and pulse volumes
beginning within 5 minutes after intravenous administration of the drug and
reaching maximum values by the end of 15 or 20 minutes. However, the rate
of increase of digital blood flow was co~iderabl~r slower as compared to pulse
and digital volumes, and m~imum values for blood flow usually occurred by
the end of 30 to 40 minutes or even longer (Fig. 3). Pulse volume always had
leveled off and frequently was decreasing before the greatest elevation of blood

C6

     50 ME. IV
120-     t ARTERIAL PRESSURE - MM. HG

loo-

eo-

60-

       HEART RATE
    72 71 D. wo se 92 68 90 92 90 86 al)
       DIGITAL VOLUME-PER CENT RISE
15 -
I!!? :

.CES-      PULSE VOLUME-CC/IO CC.

015 .
DOS-
:-      BLOOD FLOW - CC./IO CC /MIN.
;-
I -    ? *  ?? ?
  CONTROL IO 20 30 40

          TJME -MINUTES

FIG. 3. Chart of the femoral arterial pressure, heart rate, digital volume, pulse volume
and blood flow before and after the intravenous injection of 50 mg. of C6 ion in subject
P. S. The middle line in the chart of arterial pressure represents the mean arterial pressure.
The maximum increases in digital and pulse volumes precede the maximum increase in
blood flow.

flow had occurred. A similar sequence was observed after lumbar block although
the time of onset, and of maximum values occurred slightly later. Thus, block-
ade of sympathetic vasoconstrictor impulses to the digit, whether by CG or
lumbar block, always produced a rapid and early increase in pulse volume and
more gradual increase in blood flow.

Direct observations of the conjunctival vessels were made before and after C6
using a dissecting microscope. While magnification was not sufficiently high
to observe details of capillaries or to identify arteriovenous anastomoses, changes
in the venules and arterioles were readily discerned (Fig. 4). Within 10 minutes
after the intravenous administration of CG there was a marked increase in the
size of and pulsations in the larger arterial vessels. Smaller arteriolar branches
also became readily visible. At the end of 20 minutes there was an increase in


HEMODTNAXIC CHANGES              417

ILL* number of the smallest vessels visible and concurrently pulsations in the
I:lrger arterial vessels became fainter. After 30 minutes the larger arterial vessels
],:l(L decreased in size and pulsations were less readily visible. At the same time
,bcre was a marked increase in the number of small vessels with formation of
;I (tense network. ;It this time the veins greatly exceeded in size the larger

CONTROL            6 MIN. AFTER C6

L

FIG. -4. Photographs of the hulbar conjunctiva taken before and at intervals of 6, 30
and 45 minutes after the intravexlous injection of 50 mg. of CT6 ion in subject J. McG., age
80 !~ears. h large vein drains the area from left to right and is accompanied by an artery
\\hich is only faintly visible during the control period. Six minutes after C6 the artery
and its branches have become much larger, while in the later photographs the network of
smaller vessels has increased greatly in estent and the artery again has become faintly vis-
ible. See test for further details.

arterial vessels which accompanied them. Later at the end of 45 minutes. the
network of small vessels was even denser than previously. The veins became
somewhat larger but, even more striking was the decrease in the size of the
arterial vessels to a point where they were barely visible (Fig. 3).
E$ect of Infruar~cr~u~ Prismline on the D~g~~~l P~~~~~~~~~~~ and C~j~~~~~~~
                  Blood Vessels

ITThen 50 mg of Priscoline xere injected over a period of 4 minutes into the
femoral artery of the extremity under study there was only a slight increase


418            JOHNSON, FREIS AND SCHNAPER

in pulse volume to an average maximum of 0.12 cc per 10 cc of tissue after 5
minutes. The rate of blood flow likewise showed very little increase and reached
after 15 minutes an average maximum of only 1.1 cc per 10 cc per minute. By
contrast to these minor changes in pulse volume and blood flow there occurred
within 7 minutes a rapid and marked increase in digital volume comparable
to that which occurred after C6 (Table I, Fig. 5). The striking increase in digital
volume was continguous with the period of intense flushing of the skin observed
after intraarterial Priscoline. This degree of flushing F\-as not observed after C6
or epidural block.

       PRfSCOLlNE
      SOffi.LA
120-     t ARTERIAL PRESSURE- MM. HG
`II- -
60- zy----
         HEART RATE
    e* 6% so 52 s-2 96 loo too 100 96 96 92
        DIGITAL VOLUME-PER CENT RISE
?a: _            -

025 -      WLSE VOLUME - CC./ IO CC.

a5 -

:-      BLOOD FLOW -CC./IO CGIMIN.
t-
I -    I .   II I    a     I
CONTROL IO 20 30 40
      Tit&E-MINUTES

FIG. 5. Chart of the femoral arterial pressure, heart rate, digital volume, pulse volume
and blood flow before and after the intraarterial injection of 50 mg. of Priscoline in subject
R. B. Comparison with changes after C6 in this subject (See Fig. 1) indicate far less
increase in pulse volume and blood flow after Priscoline, yet digital volume rose to values
approximating those observed after CtL

Direct observation of the bulb&r conjunctival vessels with a dissecting micro-
scope was made after intravenous injection of 50 mg of Priscoline. At the end
of 10 minutes, and during the time that facial flushing was present, there was
an increase in the size of the large venous channels. Small straight branches
extending from the largest vessels became visible. After 15 minutes there was
a further slight accentuation of these changes and some increase in the number
of small vessels with fo~ation of a vascular network. The degree of increase
in vascularity was far less than that seen after C6. At the end of 25 minutes
there was very little change as compared to 15 minutes and by 35 minutes
there was a definite decrease in the number of the smallest vessels. Although
the larger venous channels still appeared distended, all other visible vessels
had diminished in size.


HEMODTNXMIC CHANGES               419

DISCUSSION

Digits1 pulse volume frequently has been employed as an index of blood flow
if) the digit, (12, 13). Tinder certain conditions a constant relationship between
these two fa&ors may exist, but under the conditions of the present studies
illcreases in pulse volume could not be int.erpreted as denoting a proportionate
increase in blood flow. When C6 and lumbar epidural block were compared
for their effects on the digital plethysmogram it was found that maximum
pulse volume in t,he toe always was 5 to $ greater after epidural block than
after CG although blood flow was increased to essentially the same degree after
(Lither procedure. Had the pulse volume alone been used to estimate blood flow
it would have been erroneously concluded that blood flow was consistently
nmch greater after lumbar epidural block than after C6. Other studies in this
laboratory (14) have disclosed a similar discrepancy between pulse volume
:md blood flow in the finger after C6 as compared to stellate block.

Since blood flow was the same both after C6 and after epidural block with
Metycaine, it was obvious that pulse volume is related to factors other than
Mood flow alone. Thus, (1) pulse volume is, `in actuality, a reflection of changes
in the larger arterial vessels since pulsatile flow does not occur beyond the
terminal arterioles, and (Z), it undoubtedly is related to p&se pressure since
the greater the spread between systolic and diastolic pressure, the more bound-
ing will be the pulse. Since hesamethonium, unlike epidural block produced a
marked reduction in pulse pressure it was reasonable to believe that this was
the major factor in the production of the smaller pulse volume following C6
as compared to epidural block.

It was noted that the early increase in digital pulse volume after sympathetic
blockade produced either with CG or epidural injection of Metycaine could not
be explained by changes in arterial pulse pressure alone because the period of
greatest pulse volume occurred at the time when the pulse pressure was the
smallest.. Likewise the early elevation of pulse volume occurring after C6 or
cpiclural block could not, have resulted from a sudden release of peripheral
resistance since blood flo~v did not reach maximum values until 15 or more
minutes later. Some ot,her local change must have occurred to make tzhe flow
more pulsatile.

The early and marked increase in digital pulse volume seemed best explained
by assuming that the initial change following sympathetic blockade is a dilata-
tion of the larger vessels on the arterial side and of the arteriovenous anastomoses
rather than of the capillaries. By restricting blood flow primarily to the larger
vessels the force of the pulse pressure would not be damped out by passage
through the more minute vessels. Further support of the concept of primary
dilatation of the larger vessels and more direct communication between arteries
and veins is furnished by previous observations that following another "sym-
patholytic" agent, dihydroergocornine (DHO), perceptible pulsations appeared
in the venous pressure recordings taken from an antecubital vein at the time
of increase in pulse volume in the finger (15).

It is also necessary to explain the later occurrence of a further increase in
blood flow without change or a slight decrease in pulse volume following sympa-


420         Y&NSON, FREIS AND SCHNAPER

thetic blockade. In order to explain the relatively late increase in blood flow
one must postulate a further decrease in peripheral resistance. Such could he
accomplished if at this later stage there occurred a relaxation of the precapil-
lary sphincters. Such an event would not only result in a greatly augmented
blood flow but also would dampen out the increased pulse volume since passage
through these small channels would convert the pulsatile flow into a more
continuous stream.

From the analysis of sequential plethysmographic changes, therefore, it, was
inferred that the earliest major change collowing sympathetic blockade either
with C6 or lumbar epidural anesthesia was dilatation of the arteries! arterioles
and A-V anastomoses. At a later stage there occurred dilatation of a masimal
number of precapillary sphincters. During the entire process of small vessel
relaxation there must have been an accelerated decline in local peripheral
resistance which reached its lowest value at the time of greatest dilatation of the
precapillary sphincters. Both after epidural block and CC, a similar pulse rolume-
blood flow pattern was observed in relation to time with the greatest increase
in pulse volume initially and later the m&mum increase in digital blood flow.

Direct observation of the conjunctival vessels supported the inferences based
on plethysmographic data. It was quite apparent t,hat the larger arterial vessels
dilated first, and only later did the "capillary lake" open up resulting in a
rapid draining away of blood from the arterial supply. The early increase in
size of the arterial vessels and the observation of increased pulsations therein
coincided with the time of maximum increase in pulse and digital volumes ob-
served in the plethysmogram, whereas the later appearance of a dense network
of small vessels coincided with the time of maximum digital blood flop.

The small increase in digital blood flow which occurred after Priscoline indi-
cated only a slight decrease in peripheral resistance. Similarly, the slight in-
crease in pulse volume suggested that there was a minor degree of dilatation
of the larger arterial vessels capable of carrying a pulsatile type of flow. How-
ever, a loss of venous tone and distention of the venous plexuses would account
for %he marked increase in digital volume. According to Sir Thomas Lewis the
skin color is determined primarily by the amount of blood in the subpapillary
venous plexuses. The period of intense flushing of the skin after Priscoline
coincided in time with the period of rapid increase in digital volume and ap-
peared to furnish further evidence for the validity of the plethysmographic
analyses.

When the changes in the vessels of the bulbar conjunctiva were observed
after Priscoline, it was seen that there was only slight dilatation of the vessels
on the arterial side without visible pulsations. In addition the appearance of a
dense network of small vessels such as was observed after C6 did not occur
after Priscoline. The most marked change observed after Priscoline was dilata-
tion and engorgement of the larger venous channels. From these observations
of plethysmographic changes and visualization of the conjunctival vessels it
is suggested that the primary action of Priscoline in the skin is on the venous
side of the circulation and hence probably is not a result. of the adrenergic
blocking effects of the drug but rather of its histaminic action.


HEJIODTNhMIC CHANGES               421

The roncepts developed in this paper are not advanced as established facts
I)ut rather as hypotheses to serve as footholds for further investigation. Certain
l)~~enornena which we have observed t,o occur in consistent patterns have been
;ubjected to analysis in the light of our present knowledge of the terminal
,~irculntion. It is hoped that analysis of the differential changes occurring in
ihe digital plethysmogram followed by correlation with data obtained using
other techniques such as direct microscopic observations may provide a method
of studying the hemodynamics of the small cutaneous vessels in man.

SUMMARY AND CONCLUSIONS

Sequential changes occurring in the digital plethysmogram after administra-
tion of hesamethonium (C6), lumbar epidural block and Priscdine given intra-
:Irterially were analyzed in terms of the hemodynamics of the small vessels of
the skin. The vasculature of the b&bar conjunctiva was observed directly to
confirm the changes of small vessels inferred from plethysmographie data.

1. Comparison of digital pulse volume and blood flow after sympathetic
blockade indicated that, pulse volume is not a reliable qu~t~~tive index of
blood flow under these conditions. Pulse volume appeared to vary primarily
with pulse pressure and dilatation of the larger vessels on the arterid side.

2. The plethysmographic cbhanges after sympathetic paralysis either with
CG or epidural block followed a constant pattern with an early increase in
digital volume and pulse T-olume to maximum values and later a maximum
incarease in digital blood flow. This plethysmographic pattern was interpreted
2s indicating an early dilatation of arteries, arterioles and A-V anastomoses
followed later by relaxation of the precapillary sphincters. Direct observa;tion
of conjunctival vessels supported the concept of early relaxation and appearance
of pulsations in larger arterial vessels and a later dilatation of the smaller vessels.

3. While pulse volume and blood flow were increased only slightly follow-
ing the injection of Priscoline into the femoral artery, there was an early striking
inrrease in digital volume coinciding in time with the marked flushing of the
skin produced by this drug. The changes in the conjunctival vessels following
Priscoline intravenously were much less marked than after C6 and were limited
mainly to the venous channels. This pattern of change was ~terpre~ as indi-
cating that Prisroline acts primarily on the venous channels of the skin.

-1. ,Analysis of differential alt,erations in the digital plethysmogram in rc?-
sponse to acute changes such as are induced by drugs, when correlated with
observations using other techniques such as direct microscopic observation
of vascular reactions, may provide a method for studying the hemodynamie
changes of the small vessels in man.

ACKNOWLEDGEMENT

The authors are indebted to Mr. Victor R. Landi for preparation of the
photographs.
                     BIBLIOGRAPHY

1. LEWIS, THOK~S: The Blood Vessels of the Human Skin and Their Responses, p. 34,
  London, 1937, Shaw and Sons, Ltd.


422            JOHNSON, FREIS AND SCHNAPER

2. LANDIS, E. M.: Micro-injection studies of capillary blood pressure in human skin,
  Heart, 15: 209, 1930.

3. CHAMBERS, R. AND ZWEIFACH, B. W. Functional activity of the blood capilIary bed,
with special reference ta visceral tissue, Ann. Skew York Acad. SC., 46: 683, 1946.
4. LUTZ, B. R., FULTON, G. P. AND AKERS, R. P., The neuromotor mechanism of the small
  blood vessels in membranes of the frog (Rana pipiens) and the hamster (Mesocrieetus
  auratus) with reference to the normal and pathological conditions of blood flow,
  Exper. Med. and Surg. 8: 258,1950.

5. CHAMBERG, R. AND ZWEIFACH, B. W. Topography and Function of the mesenteric capil-
  Iary circulation. Am. 3. Anat., 76: 173, 1944.

6. CURE, R. Arterio-venous anastomoses. Physiol. Rev., 18: 229, 1938.
7. BURCH, G. E. A new sensitive portable plethysmograph. .4m. Heart J. 33: 48, 1947.
8. ROBERTSON, C. W., FARMER, D. A. AND SXITHVI.ICX, R. H. A simplified venous occlusion
  method of digit blood flow estimation using the Burch-Winsor plethysmograph. J.
  Lab. and Clin. Med., 34: 1718, 1949.

9. GOETZ, R. H.: The rate and control of the blood flow through the skin of the upper
  extremities. S. Afr. J. Med. SC., 8: 65,1943.

IO. FREIS, E. D., SCKNAPER, H. W., JOHNSON, R. L. AND SCHREISER, G. E. Hemodynamic
  alterations in acute myocardial infarction. I. Cardiac output, mean arterial pressure,
  total peripheral resistance, "central" and total blood volumes, venous pressure
  and average circulation time. To be published.

11. SCHNAPER, H. W., JOBNSON, R. L., TOUHY, E. B. ?LND FREIS, E. D. The effect of hess-
  methonium as compared to procaine regional block on the blood flow to t,he foot, of
  normal subjects. J. Clin. Investigation. In press.
12. HERTZMAN, A. B., RANDALL, W. C. AND Jocmnr, I(. E.: The estimabion of the cutaneous
  blood flow with the photoelectric plethysmograph. Am. J. Physiol., 146: 716, 1946.
13. BURTON, A. C.: The range and variability of the blood flax in the human fingers and
  the vasomotor regulation of body temperature. Am. J. Physiol., 127: 437, 1939.
14. JOHNSON, R. L., SCHNAPER, H. W. AND FREIS, E. D.: Unpublished data.
15. FREIS, E. D., STANTON, J. R., LITTER, J., CULBERTSOX, J. W., HALPERIS, hl. H., Mars-
  TEE, F. A. AND WILKINS, R. W.: The hemodynamic effects of hypotensive drugs in
  man. II. Dihydroergocornine. J. Clin. Investigation, 28: 1387, 1939.