bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of oscillatory and unidirectional flows in straight tubes and an airway cast
Authors: Dorkin H. L. , Jackson A. C. , Strieder D. J. , Dawson S. V.
Published: December 2017

Because oscillatory resistance of the respiratory system is often measured during tidal breathing, we studied the interaction between simultaneous oscillatory and unidirectional flows in three straight tubes (radius ranging from 0.3025 to 0.679 cm and length either 30.7 or 173 cm) and a central airway cast (tracheal radius 0.685 cm). Oscillatory flow was generated by a loudspeaker, airway pressure was measured with a transducer, and flow was calculated from pressure changes in an airtight enclosure mounted behind the flow source (loudspeaker plethysmograph). Oscillatory resistance, i.e., the real part of impedance, was determined from 2 to 64 Hz. In the absence of unidirectional flow, frequency dependence of resistance was observed for the two 30.7-cm-long tubes to match previously published theory. Frequency dependence of resistance for the airway cast was similar to that of the tube of comparable inlet radius. In the presence of unidirectional flow, oscillatory resistance at low frequency was independent of frequency and determined by the magnitude of the unidirectional flow. Oscillatory resistance at high frequency was frequency dependent but still influenced by the magnitude of the unidirectional flow. Our results indicate that the presence of unidirectional flow alters the oscillatory resistance of tubes and the cast at any given frequency, presumably by changing the shape of the boundary layer.
Response of the pulmonary circulation to acute hypoxia in the growing pig
Authors: Rendas A. , Branthwaite M. , Lennox S. , Reid L.
Published: December 2017

In a previous article we have analyzed the structure of the growing pig lung and correlated the findings with cardiorespiratory function studies on the same animals (J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 45: 806–817, 1978). The present study analyzes the pulmonary and systemic vascular responses to acute hypoxia in some of those animals at three ages, 2–4, 5–8, and 9–12 wk, the lung of the 12-wk-old pig being structurally similar to that of the adult. In all anesthetized animals, acute hypoxia (5 min 10% fractional inspired oxygen concentration) increased mean pulmonary arterial pressure (Ppa) and total pulmonary resistance (TPR). The increase over base line of Ppa was 41.3% in animals aged 2–4 wk; 83.0% in those aged 5–8 wk, and 136.9% in those aged 9–12 wk; for TPR the increase in the three age groups was 66.4, 92.4, and 138.9%, respectively. This difference in vasoactivity with age is associated with the progressive extension of smooth muscle into the intra-acinar arterial tree, which we have previously shown is an important feature of the structural remodeling that occurs during postnatal lung development in both man and swine.
Exponential analysis of pressure-volume relationship in excised human lungs
Authors: Berend N. , Thurlbeck W. M.
Published: December 2017

Eighty excised human lungs were placed in a volume-displacement plethysmograph, and expiratory pressure-volume (PV) data points were obtained between transpulmonary pressures of 30 and 0 cmH2O. An exponential function of the form V = A - Be-KP was fitted to the PV data points (V is the volume at pressure P, A is the maximal lung volume at infinite pressure, B is A minus the intercept of the exponential on the volume axis, and K is a shape constant directly related to lung compliance). Thirty-two lungs were emphysema-free and 48 lungs had emphysema ranging from grade 2 to grade 80. In the emphysema-free lungs the exponential fit was excellent in terms of r2, but systematic deviations from the PV data occurred in both young and old lungs. Both K and B/A were significantly age related (P less than 0.01). In the emphysematous lungs the exponential fit was equivalent to that in the emphysema-free lungs although, again, systematic deviations from the PV data occurred. With age constant, K (P less than 0.01) but not B/A was significantly correlated with the emphysema grade. However, the overlap with values of K in the emphysema-free lungs was too great for K to be useful in the diagnosis of emphysema.
Thermal insulation and shivering threshold in Greek sponge divers
Authors: Veicsteinas A. , Rennie D. W.
Published: December 2017

Sublingual temperature (Tor), average skin temperature (Tsk), and skin heat flow (Hsk) were determined in a field study for six Greek sponge divers and seven nondiving controls during head-out immersions at water temperature of 21 degrees C. Wetsuits kept Tsk at 22–28 degrees C for 1–3 h until Tor fell to 36.5–35.5 degrees C and violent shivering [metabolic rate (M) = 100–150 W . m-2] ended the test. At a steady Tsk, immediately before shivering, overall tissue insulation (It), calculated as (Tor--Tsk)/Hsk, was linearly related to mean subcutaneous fat thickness (MFT) in both groups without statistical difference between them. The onset of shivering, as detected by a sharp increase of M, occurred at the same Tor for a Tsk of about 26 degrees C, and the relationship of M vs. Tor (i.e., metabolic sensitivity) was the same for both groups. Contrary to other groups accustomed to diving in cold water, the use of a wetsuit for a long time has evidently prevented cold adaptation in these divers.
Effect of upper body posture on forced inspiration and expiration
Authors: Haas F. , Simnowitz M. , Axen K. , Gaudino D. , Haas A.
Published: December 2017

The upper body posture naturally adopted by long distance runners was quantified, and its effects on ventilation were assessed in 14 subjects. Maximum voluntary ventilation (MVV) and flow-volume loop maneuvers were performed in three seated positions: 1) natural running posture (RUN), with back angled forward 11 degrees, neck flexed, and head extended 35 degrees forward of the spinal column; 2) back vertical with head and neck as above (NEF); and 3) head and back vertical (VERT). MVV was significantly higher in RUN compared with both NEF and VERT, as were peak inspiratory pressure (PImax) from functional residual capacity, peak expiratory flow (PEF), and peak inspiratory flow (PIF). Expiratory flow at 50% of vital capacity was significantly higher in RUN and NEF than in VERT, consistent with reported increases in flow due to tracheal stiffening. The increased PIF and PImax in RUN indicate increased inspiratory muscle tension and/or improved transduction of tension into a more negative pleural pressure. Magnetometer tracings of rib cage dimensions demonstrated greater anteroposterior stability during maximal inspiratory efforts in RUN compared with VERT. The improved inspiratory function seen in RUN may be due to more effective diaphragmatic and/or accessory muscle function. These findings demonstrate that the position naturally adopted by long distance runners favors ventilation.
Regional effects of autonomic agents on ion transport across excised canine airways
Authors: Boucher R. C. , Gatzy J. T.
Published: December 2017

The effects of cholinergic and adrenergic agonists and antagonists on ion transport and bioelectric properties of excised canine trachea, main-stem bronchi, and subsegmental bronchi were studied. Acetylcholine (ACh) induced in bronchi a dose-dependent reduction in net Na+ absorption, maximal (30%) at 10(-5) M, that reflected a raised Na+ flux from submucosa to mucosa. Because conductance (G) did not change we speculate that the increased flow in the “passive” direction represents the induction of bidirectional Na+ transport. ACh (10(-4) M) increased net Cl- secretion in the trachea and main-stem bronchi and reduced Na+ absorption. ACh effects in all regions were blocked by atropine. In bronchi, alpha- or beta-adrenergic agonists, 10(-5) and 10(-3) M, raised G and unidirectional Cl- fluxes without affecting short-circuit current (Isc) or inducing Cl- secretion. Small reductions in Na+ absorption were noted at 10(-5) M. In contrast, adrenergic agents increased Isc and Cl- secretion in the trachea. We concluded that neurohumoral agonists induce different patterns of effects on ion transport in central compared with more distal airways. Agonists of both classes induced Cl- secretion in the trachea and reduced but did not abolish net NaCl absorption in the bronchi.
Delayed kinetics of respiratory gas exchange in the transition from prior exercise
Authors: Hughson R. L. , Morrissey M.
Published: December 2017

The kinetics of oxygen uptake (VO2), carbon dioxide output (VCO2), and expired ventilation (VE) in the transition from rest or from prior exercise were studied in response to step increases in power output (PO). The data were modeled with a single-component exponential function incorporating a time delay (TD). Each subject exercised on four occasions. Test 1 was an incremental test for determination of ventilatory anaerobic threshold (AT). Step increase tests were rest to 80% of PO at AT (test 2), rest-40% AT (3a), 40–80% AT (3b), rest-40% AT (4a), and 40–120% AT (4b). Respiratory gas exchange was monitored by open-circuit techniques. The VO2 kinetics showed the time constant (tau) to be longer in the transitions from prior exercise [tests 3b and 4b were 60.6 +/- 10.8 (SD) and 79.2 +/- 17.4 s] than from rest (tests 2, 3a, and 4a were 37.8 +/- 7.2, 30.0 +/- 7.8, and 39.6 +/- 17.4 s). The mean response time (MRT = tau + TD) was also longer for these tests. Kinetic analysis for VCO2 showed a tendency for tau to be shorter for the tests from prior exercise, but neither tau nor tau + TD were significantly different between tests. In contrast to VCO2, VE kinetics showed a significantly longer tau + TD for test 3b (P less than 0.05) and test 4b (P less than 0.01). This study has shown the VO2 kinetics to be delayed when a given increment in PO occurred from prior exercise, whether the final PO was below or above the AT. Further, the dissociation of VCO2 and VE kinetics does not support a direct link between these two variables as the sole control factor in exercise hyperpnea.
Force-velocity relationship of expiratory muscles in normal subjects
Authors: Kikuchi Y. , Sasaki H. , Sekizawa K. , Aihara K. , Takishima T.
Published: December 2017

We examined the force-velocity relationship of the respiratory muscles in normal subjects under nearly isotonic conditions, taking into consideration the pleural pressure (Ppl) changes during maximum forced expirations (MFE). We used an electromagnetic valve (EMV) to select the Ppl value at the onset of mouth flow; and both a pressure reservoir and a variable resistance to control the Ppl changes after the opening of the EMV during MFE. To simulate isotonic conditions and to obtain the shortening velocity of the contractile element (CE), we mathematically corrected the velocity of the series elastic component (SEC), using a modified version of Hill's equation. Although the maximum tension at total lung capacity (TLC) [1,156 +/- 215 (SD) g/cm] was larger than that at functional residual capacity (FRC) (782 +/- 97 g/cm) there was no significant difference in the maximum shortening velocity, 3.4 +/- 1.0 and 3.2 +/- 0.8 circumference/s at TLC and FRC, respectively. The mean values of k (slope) for the SEC at TLC and FRC were 19 +/- 4 and 18 +/- 5 circumference-1, respectively, and they were not significantly different. We concluded that the force-velocity relationship of the expiratory muscles exhibited the same mechanical properties as that of the other skeletal muscles.
Demonstration of failure of body plethysmography in airway obstruction
Authors: Rodenstein D. O. , Stanescu D. C. , Francis C.
Published: December 2017

To demonstrate the role of extrathoracic airways in the overestimation of lung volumes by body plethysmography in airway obstruction, we induced in six normal subjects an artificial airway stenosis by inflating a balloon in the lower trachea. We measured thoracic gas volume in a body plethysmograph simultaneously from mouth pressure (Pm) vs. plethysmographic volume (Vbox) (TGVm) and from esophageal pressure (Pes) vs. Vbox (TGVes). During control measurements there was no difference between TGVm and TGVes (P greater than 0.1) in any subject. Balloon inflation (B) resulted in a significant (P less than 0.01) decrease of specific airway conductance (sGaw) from a mean value of 0.199 +/- 0.66 (SD) to 0.025 +/- 0.01 cmH2O-1 . s-1. TGVm significantly (P less than 0.02) exceeded TGVes in every subject (mean diff 1.24 +/- 0.56 liters) and Pm lagged behind Pes. In two subjects studied at different levels of airway obstruction we found a significant (P less than 0.05) correlation between TGVm-TGVes difference and sGaw. Bypassing the extrathoracic airways by a cuffed endotracheal tube resulted in each case in a degree of airway obstruction comparable to that during balloon inflation (sGaw 0.019 +/- 0.004 cmH2O-1 . s-1), but no difference between TGVm and TGVes (P greater than 0.1). We conclude that lung volume is overestimated by plethysmography in airway obstruction. The overestimation is due to the presence of a compliant extrathoracic airway, and it probably depends on both the degree of airway obstruction and the value of compliance of the extrathoracic airway.
Interaction of serotonin with vagal- and ACh-induced bronchoconstriction in canine lungs
Authors: Sheller J. R. , Holtzman M. J. , Skoogh B. E. , Nadel J. A.
Published: December 2017

The bronchoconstrictor response to electrical stimulation of the peripheral ends of both cut cervical vagus nerves was potentiated by serotonin aerosols in 10 experiments in 7 anesthetized dogs. The bronchoconstrictor response to acetylcholine (ACh) aerosols was unchanged after serotonin. We conclude that serotonin acts at the level of the parasympathetic ganglia or the postganglionic nerve terminal to potentiate the bronchoconstrictor response to vagal stimulation.
Effect of limb immobilization on skeletal muscle
Authors: Booth F. W.
Published: December 2017

The immobilization of limbs resulted in atrophy of those muscles that are fixed either at or less than resting length. The loss in protein in these muscles can be described by a first-order equation. Decreases in protein synthesis rate in muscles of immobilized limbs occur during the first 6 h of immobilization, and this decrease probably played a role in initiating muscular atrophy. After weeks of immobilization, muscles composed predominately of slow-twitch fibers took on properties characteristic of fast twitch muscles. The EMG activity of muscles in immobilized limbs was reduced to 5--15% of control levels. Insulin responsiveness for 2-deoxyglucose uptake into the soleus muscle of a limb is decreased at the 24th h of limb immobilization. Muscles of immobilized limbs have either no change or a decrease in resting membrane potential, an increase in extrajunctional acetylcholine receptors of lesser magnitude than the increase that occurred in denervated muscle, and no change in acetylcholinesterase activity in neuromuscular junctions. Immobilizing muscles at stretched lengths prevented the decrease in nerve afterhyperpolarization that was seen in muscles immobilized at shortened positions. These observations suggested that metabolic changes in muscles have a retrograde trophic influence on motor nerves. The model of limb immobilization permits the study of many fundamental problems concerned with mechanisms by which a muscle adapts so that it can meet the requirements of the external environment.
Effects of hyperventilation on pulmonary blood flow and recirculation time of humans
Authors: Matalon S. , Dashkoff N. , Nesarajah M. S. , Klocke F. J. , Farhi L. E.
Published: December 2017

We used direct invasive techniques to measure the effects of hyperventilation on the pulmonary blood flow (Q) and on recirculation time of helium and of carbon dioxide in humans. The subjects hyperventilated with a tidal volume of 1.5 liters (BTPS) and a frequency of 20 or 30 breaths/min. There was no significant change in Q from control at either level of hyperventilation. Helium first appeared in the pulmonary artery within 12 s from the onset of hyperventilation and increased by approximately 0.7% of its equilibrium arterial value per second at both levels of hyperventilation. In contrast, the PVCO2 remained at base-line level until 43 s from the onset of hyperventilation. We conclude that hyperventilation at 30 or 45 l/min with constant tidal volume does not significantly affect the value of Q and that the amount of recirculation of the two gases does not result in underestimation of Q when this variable is measured by indirect respiratory rebreathing techniques.
Blood-gas CO2 equilibration in lungs of unanesthetized dogs during hypercapnia
Authors: Jennings D. B. , Meyer M. , Stokke T. , Piiper J. , Scheid P.
Published: December 2017

We have reinvestigated the problem of blood-gas equilibration of CO2 in lungs during hypercapnia. Six dogs with chronic tracheostomy and exteriorized carotid artery were subjected in acute experiments to hypercapnic inspired mixtures [CO2 fraction of expired gas (FICO2) = 0.06; 0.08; 0.10]. Expired CO2 partial pressure (PCO2) was continuously measured with a respiratory mass spectrometer and compared with arterial PCO2 determined in blood samples that were collected during apparent steady-state conditions. Particular care was taken in using continuously recorded temperature in the right heart for correction of blood PCO2 measured by CO2 electrodes. In no animal was there a significant difference between arterial and alveolar PCO2. On the average, this difference was -0.1 Torr at FICO2 = 0.06; 0.0 Torr at FICO2 = 0.08, and -0.2 Torr at FICO2 = 0.10. The results are in agreement with the conventional view that PCO2 in pulmonary capillary blood approaches PCO2 in alveolar gas.
Acute hypervolemia, cardiac performance, and aerobic power during exercise
Authors: Kanstrup I. L. , Ekblom B.
Published: December 2017

The relative importance of blood volume (BV) for the maximum aerobic power (VO2 max) was evaluated in healthy subjects by sequential measurements without intervention under two conditions: 1) after hemodilution with a plasma expander, thus increasing BV but keeping red cell mass constant and lowering hemoglobin concentration [Hb], and 2) after whole blood withdrawal, which restored BV to control conditions but reduced red cell mass and [Hb] to equal conditions under 1. After BV expansion (avg 700 ml), we found an unchanged VO2 max compared with control data despite lowered [Hb]. Cardiac output (Q) was increased after BV expansion at rest and during all exercise levels (maximum 27.4 and 29.5 l . min-1, respectively). Peak stroke volume was increased from 144 to 173 ml. Arterial blood pressures were either unchanged or lowered. In contrast, after blood letting to a similar [Hb], we found a significantly reduced VO2 max. These findings indicate a significant influence of the size of the blood volume on cardiac performance. The increased Qmax is discussed in relation to preload, inotropic state, heart rate, and afterload. Plasma volume expansion causes increased preload which may explain this primary effect on the central circulation (Frank-Starling effect).
Dynamics of breathing in infants
Authors: Mortola J. P. , Fisher J. T. , Smith B. , Fox G. , Weeks S.
Published: December 2017

Passive compliance (C) has been measured in 10 infants at 10--90 min after birth and in 10 infants at a few days of life by recording mouth pressure after airways occlusions at end inspiration. From the slope of the expiratory flow-volume curve, the passive time constant (tau) and resistance (R = tau/C) have been also computed. Examination of the changes of C with time and of the expiratory flow-volume curves indicates that the end-expiratory volume is maintained above functional residual capacity at both ages, but significantly more so at a few days (7.6 ml) than at 10--90 min (3.5 ml). The passive time constant (tau = C . R) is shorter at the early age due to the smaller C. The active compliance (C′) and resistance (R′) values have been estimated from the pressure generated by the infant when the airways are occluded at end expiration. The active time constant of the respiratory system (tau′ = C′ . R′) is less than tau, due to a smaller active compliance, particularly at a few days. The active resistance is on the contrary similar to R. The active stiffening of the respiratory system provides more stability of the infant's respiratory system and a more ready volume response for any given change in pressure; its price, however, is a higher work of breathing. At optimal breathing rates, in fact, the active work is 127% (10--90 min) to 183% (a few days) higher than that computed from the passive values. The inspiratory flow wave tends to be squared at both ages minimizing the energy losses due to friction.
Increases in plasma beta-endorphin/beta-lipotropin immunoreactivity after treadmill running in humans
Authors: Farrell P. A. , Gates W. K. , Maksud M. G. , Morgan W. P.
Published: December 2017

Six well-trained endurance athletes were studied to determine if submaximal treadmill exercise results in increased plasma levels of beta-endorphin/beta-lipotropin (Bh-Ep/Bh-LPH) immunoreactivity. Bh-Ep/Bh-LPH immunoreactivity was measured by radio immunoassay in plasma from six experienced runners before and after 30-min treadmill runs at a self-selected pace, 60 and 80% VO2 max, and a control experiment of 30 min rest. All tests were randomized and occurred during the same time of day for a given subject (0600--1500 h). Preexercise Bh-Ep/Bh-LPH values averaged between 10 and 20 pg/ml and increased two- to fivefold after each run. The increase was statistically significant (P less than 0.05) only after the 60% run when Bh-Ep/Bh-LPH increased to a mean of 58.3 pg/ml. A large individual variation in the Bh-Ep/Bh-LPH response to running was noted. Mood state and perceptual data were also collected, and no significant relationship with Bh-Ep/Bh-LPH was evident. These data suggest that the stress of treadmill running acts as a stimulus to greater Bh-Ep/Bh-LPH secretion, a reduction in its degradation, or a combination of these, which leads to increased levels of these ligands in venous blood. The physiological significance of these increased plasma levels is not clear.
Intrapulmonary Co2 receptors and ventilatory response to lung Co2 loading
Authors: Tallman R. D. , Grodins F. S.
Published: December 2017

The possible role of intrapulmonary CO2 receptors (IPC) in arterial CO2 partial pressure (PaCO2) homeostasis was investigated by comparing the arterial blood gas and ventilatory responses to CO2 loading via the inspired gas and via the venous blood. Adult male Pekin ducks were decerebrated 1 wk prior to an experiment. Venous CO2 loading was accomplished with a venovenous extracorporeal blood circuit that included a silicone-membrane blood oxygenator. The protocol randomized four states: control (no loading), venous CO2 loading, inspired CO2 loading, and venous CO2 unloading. Intravenous and inspired loading both resulted in hypercapnic hyperpnea. Comparison of the ventilatory sensitivity (delta VE/delta PaCO2) showed no significant difference between the two loading regimes. Likewise, venous CO2 unloading led to a significant hypocapnic hypopnea. Sensitivity to changes in PaCO2 could explain the response of ventilation under these conditions. The ventilatory pattern, however, was differentially sensitive to the route of CO2 loading; inspired CO2 resulted in slower deeper breathing than venous loading. It is concluded that IPC play a minor role in adjusting ventilation to match changes in pulmonary CO2 flux but rather are involved in pattern determination.
Effects of intracranial and left atrial hypertension on lung fluid balance in sheep
Authors: Jones T. A. , Townsley M. I. , Weidner W. J.
Published: December 2017

Elevation of intracranial pressure (ICP; 50–150 Torr) in sheep produces an increase in protein-rich lymph flow (QL) from the lung. This may be attributed to either microvascular permeability changes or increases in filtration surface area through recruitment. To eliminate increases in surface area, we recruited potential filtration beds by increasing left atrial pressure (Pla; 27–35 Torr) prior to elevating ICP in sheep anesthetized with pentobarbital sodium or halothane. Under these conditions, increased pulmonary microvascular permeability would be expected to produce an increased QL, lymphatic protein flux (CL), and plasma clearance of protein (CP). The results of ICP elevation following a period of steady-state Pla hypertension showed no such change in QL, CL or CP (n=8) compared with prior period of increased Pla. ICP elevation alone (n=6) produces a significant increase in CP manifested as an increase in QL (73%), with little change in the lymph-to-plasma ratio of protein concentration. These results suggest that a change in pulmonary microvascular surface area (not permeability) is the primary mechanism underlying increases in protein-rich QL following the elevation of ICP alone.
A computer linear regression model to determine ventilatory anaerobic threshold
Authors: Orr G. W. , Green H. J. , Hughson R. L. , Bennett G. W.
Published: December 2017

The anaerobic threshold has generally been determined by simple visual inspection of ventilation or other gas-exchange data obtained during incremental exercise. To establish objective criteria for the determination of anaerobic threshold, a computer algorithm has been developed that models the ventilatory response to exercise using multisegment linear regression. The best-fit regression model is chosen by minimizing the pooled residual sum of squares . The anaerobic threshold is reported as the first break point in that model. The computer-determined anaerobic threshold values for 37 subjects were compared with subjectively determined values as chosen by four independent observers. The observers' estimates, when pooled to yield a single a single value for each subject, gave a mean value for the gas-exchange anaerobic threshold of 2.26 +/- 0.69 l/min. The estimates by the computer method averaged 2.21 +/- 0.65 l/min. The correlation coefficient for these two methods was 0.94.
Man at extreme altitude
Authors: West J. B.
Published: December 2017

The history of man's attempts to learn more about the physiology of extreme altitudes is briefly reviewed. The earliest exploits were by balloonists who were often exposed to very severe hypoxia, sometimes with fatal consequences. A turning point was the work by Paul Bert using low-pressure chambers; he was able to prove that the deleterious effects of low barometric pressures were caused by the low PO2, though other explanations for mountain sickness such as a low aterial PCO2 continued to be promoted for some time. Many early physiologists believed that active secretion of oxygen by the lungs was necessary to explain man's tolerance of extreme altitudes. Indeed, Haldane championed this view until his death in 1936, though strong evidence to the contrary had accumulated since the work of Krogh and others in the first decade of the century. High climbs by mountaineers have stimulated much interest in the physiology of severe hypoxia. Norton reached over 8,500 m on Mt. Everest in 1924, but the summit was not attained without supplementary oxygen until 1978--the last 300 m took 54 years! This suggests that the summit, altitude 8,848 m, is very near the limit of human tolerance, and predictions based on maximal work levels measured at lower altitudes are consistent with this. The American Medical Research Expedition to Everest, 1981, was specifically planned to obtain data on human physiology at extreme altitudes, and a number of measurements were made over 8,000 m, including some on the summit itself. It is apparent that the mountain can be climbed without supplementary oxygen only because the barometric pressure at the summit is not as low as has often been predicted, and because of the extreme hyperventilation that man develops under these conditions.
Mechanical properties of the lungs during acclimatization to altitude
Authors: Gautier H. , Peslin R. , Grassino A. , Milic-Emili J. , Hannhart B. , Powell E. , Miserocchi G. , Bonora M. , Fischer J. T.
Published: December 2017

Mechanical properties of the lung were studied in nine healthy lowlanders during a 6-day sojourn at an altitude of 3,457 m. In comparison to sea-level values, it was found at altitude that 1) lung volumes measured by plethysmography including total lung capacity, vital capacity, and functional residual capacity (FRC) presented small changes not exceeding 300 ml; 2) static and dynamic lung compliances were not modified but static pressure-volume curves of lungs were shifted progressively to the left (the decrease in lung elastic recoil averaged about 2 cmH2O on days 4–6); and 3) maximal midexpiratory flow, forced expiratory volume in 1 s, and maximal expiratory and inspiratory flows were increased and, conversely, airways and pulmonary flow resistances were decreased on most days at altitude. The unchanged FRC in the face of a decreased lung recoil may be explained by an increase in thoracic blood volume at altitude, but other possible mechanisms are discussed. The decrease in resistances and increase in maximal flows may be partly explained by the decreased air density at altitude, but another contributing factor such as a bronchodilatation is also suggested. It is proposed that changes in lung mechanics at altitude may account for some of the changes in the pattern of breathing and mouth occlusion pressure (P0.1) observed during acclimatization of lowlanders to altitude.
Fetal lung in organ culture. IV. Supra-additive hormone interactions
Authors: Gross I. , Wilson C. M.
Published: December 2017

Corticosteroids, thyroid hormones, and theophylline have previously been shown to accelerate fetal lung maturation. We have examined the interactions between these agents in relation to phospholipid synthesis in explants of 18-day fetal rat lung in organ culture. Maximal stimulation of the rate of incorporation of choline into phosphatidylcholine, the most abundant phospholipid in pulmonary surfactant, was observed at a dexamethasone concentration of 100 nM. Exposure to 100 nM dexamethasone, 1.0 mM theophylline, or a combination of the two agents for 48 h resulted, respectively, in 144, 157, and 508% stimulation of the rate of incorporation of choline into disaturated phosphatidylcholine. Similar supra-additive interactions between dexamethasone and dibutyryl adenosine 3′,5′-cyclic monophosphate (cAMP) were observed, but the effects with caffeine were less striking. The increase in the rate of precursor incorporation was associated with a significant increase in the disaturated phosphatidylcholine content of the cultures. Combination of dexamethasone with 100 nM triiodothyronine (the concn producing maximal effects) also resulted in supra-additive stimulation but to a smaller degree. These findings of interactions in vitro suggest that the agents act on the lung at different biochemical sites, but the mechanisms whereby they interact at the cellular level have yet to be established. The data provide a rationale for in vivo animal studies of the effects of combined hormone administration on fetal lung maturation.
Comparison of capsular and intra-alveolar fluid pressures in the lung
Authors: Parker J. C. , Taylor A. E.
Published: December 2017

The fluid pressures measured in chronically implanted capsules were compared with fluid absorptive pressures in small degassed lung segments. Capsules were implanted, and bronchiolar catheters were placed at different vertical heights in the lungs of spontaneously breathing dogs. Increases in pulmonary capillary filtration pressure were produced by volume infusions of Tyrode's solution and increased left atrial pressure. A vertical gradient in fluid pressures was consistently observed with more negative pressures near the top of the lungs. Capsular fluid pressures averaged -7.82 cmH2O with a gradient of -0.60 cmH2O/cm distance up the lung. The intra-alveolar absorptive pressures averaged -14.4 cmH2O with a gradient of -0.78 cmH2O/cm distance up the lung. The fluid pressures in both the capsules and alveolar segments responded to changes in capillary filtration pressure (capillary hydrostatic pressure minus plasma colloid osmotic pressure). The overall change in these extravascular fluid pressures amounted to approximately 25% of the change in filtration pressure, although considerable variability in individual measurements was obtained. Because they respond to imbalances in Starling capillary forces, both the capsular and intra-alveolar fluid pressures may be considered a function of perimicrovascular tissue pressure in the lung.
Lung volume, closing volume, and gas exchange
Authors: Morrison S. C. , Stubbing D. G. , Zimmerman P. V. , Campbell E. J.
Published: December 2017

The effect of a voluntary reduction in lung volume on arterial O2 saturation (SaO2) was studied in 10 normal subjects aged 19–63 yr. SaO2 was measured by ear oximetry first during tidal breathing at functional residual capacity, and then during tidal breathing at 380 ml above residual volume. Tidal volume and breathing frequency were kept constant, and end-tidal CO2 partial pressure remained stable or fell in 9 out of 10 subjects. When lung volume was reduced, SaO2 fell by a mean of 1.5% (range 0–3%). Closing volume (CV) was measured by the N2-washout method (mean 0.89 liter, range 0.41–1.44). There was a close correlation between CV and the fall in SaO2 (r = 0.867, P = 0.001). Arterial and mixed venous CO2 were measured in one subject; the results indicated some fall in cardiac output following the lung volume change, but this accounted for less than half of the fall in SaO2. The relationship between CV and the lung volume at which tidal breathing occurs is an important determinant of pulmonary gas exchange through its effect on the matching of ventilation to perfusion.
Effects of endogenous glucagon on glucose kinetics in shivering dogs
Authors: Minaire Y. , Forichon J. , Freminet A.
Published: December 2017

Intravenous infusion of D-[3–3H]glucose at a constant rate was used to measure glucose production (rate of appearance, Ra) and utilization (rate of disappearance, Rd) in normal overnight-fasted dogs exposed to either neutral (TaN = +25 degrees C) or cold (TaC = -21 degrees C) ambient temperature. At TaC the metabolic rate was 4.1 times greater than at TaN and the dogs remained normothermic under both conditions. During control periods, cold exposure provoked a 2.2 times increase in hepatic Ra while plasma glucagon remained unaffected. Between two control periods somatostatin (1 microgram.kg-1.min-1 iv) and insulin (0.5 mU.kg-1.min-1 intraportal) were infused in such a manner that plasma insulin remained fairly constant at basal levels while glucagon dropped by 51% (TaN) and 66% (TaC), these percentages being not significantly different. This selective glucagon deficiency resulted in a 24% (TaN) and 30% (TaC) reduction in plasma glucose concentration, due to a 23% (TaN) and 25% (TaC) reduction in glucose production. There was a significant (r = 0.82, P less than 0.01) correlation between the control Ra and the reduction induced by the glucagon deficiency. At TaN and TaC, two significant parallel relationships were found between hepatic Ra and plasma glucagon concentration suggesting that glucagon has a modulatory effect on more fundamental mechanisms triggered by the cold-increased metabolic needs.
Bronchial responsiveness to inhaled methacholine in young asymptomatic smokers
Authors: Malo J. L. , Filiatrault S. , Martin R. R.
Published: December 2017

Methacholine inhalation challenges were performed in 10 young smokers who denied having respiratory symptoms and in 10 nonsmokers of the same age. There were five males and five females in each group. The bronchoconstriction was evaluated with specific lung conductance (sGL), maximum partial (initiated from end-inspiratory lung volume) expiratory flows assessed at 40% vital capacity breathing air (Vmax40p air), and a He-O2 mixture (Vmax40p He), and with maximum complete flows breathing He-O2 [forced expiratory volume at 1 s (FEV1), Vmax50c He]. Dose-response curves were studied for 1) threshold concentration (TC) where values depart by more than two SD from base line; 2) provocative concentration (PC) causing a fixed fall in a parameter. Smokers differed significantly from nonsmokers for TC and PC accessed by Vmax40p He (P less than 0.001 and P less than 0.01, respectively), Vmax40p air (P less than 0.01), and Vmax50c He (P less than 0.01 and P less than 0.05, respectively). TC and PC estimated by sGL and FEV1 were not significantly different. Males and females showed a similar reaction.
Effects of gravity and branching on longitudinal gas mixing in glass tube models
Authors: Shibata H. , Okubo T. , Fuyuki T. , Takishima T. , Imaishi N.
Published: December 2017

We investigated the effects of gravity and branching on gas mixing in glass tube models. The mixed gas (5% He and 5% SF6) was made to flow through a straight tube and tubes with bifurcated branches, and the effective axial diffusion coefficient (Deff) was measured. The direction of the branches was varied from upward to downward by 90% turns, and the flow distribution to each branch was separately controlled. In the case of a straight horiontal tube, the flow velocity dependency of the Deff of He and SF6 was observed as we expected from Aris' equation. In the case of glass tubes with branches, the Deff of SF6 was greater in the downward-directed branches than it was in the upward-directed branches when gas mixing occurred at the front of the gas mixture; however, when gas mixing occurred at the tail, the opposite effects were observed. These characteristics were more marked at slower flow rates and when the flow to each branch was different. Our findings suggest that gravity has an effect on gas mixing in glass tube airway models, especially at a low flow rate and uneven flow distribution.
Effects of testosterone propionate on hindlimb-immobilized rats
Authors: Evans W. J. , Ivy J. L.
Published: December 2017

Forty albino male rats were randomly divided into 4 groups of 10. Group I served as the nonimmobilized control and received daily placebo injections of sesame oil. The rats in group II were castrated, their hindlimbs were immobilized using a plaster cast, and they received daily injections of sesame oil. The group III rats were also castrated and casted but received a daily injection of 5 mg testosterone propionate. The animals in group IV were not castrated but were casted and received daily testosterone propionate injections. The duration of each treatment was 15 days for each rat. The gastrocnemius, quadriceps, soleus, and cardiac muscles were weighed after treatment. O2 consumption capacity (QO2), citrate synthase activities, and percentages of water were measured in the gastrocnemius, quadriceps, and cardiac tissues. Along with the atrophy of muscle and reduction in body size, the immobilization significantly reduced the aerobic capacity of affected muscle groups and cardiac tissue. The greatest reductions in body weight, muscle size, heart size, and QO2 were seen in the castrated group that received only placebo injections of sesame oil. The anticatabolic effects of the anabolic steroid were evident in groups III and IV. The results indicate that hindlimb immobilization not only causes severe atrophy in those muscles immobilized but has an overall catabolic effect on the animal. Testosterone, or the lack of it, can significantly affect the amount of muscle atrophy.
Sympathetic and parasympathetic cardiac control in athletes and nonathletes at rest
Authors: Katona P. G. , McLean M. , Dighton D. H. , Guz A.
Published: December 2017

A simple model to characterize sympathetic and parasympathetic effects on heart rate (R) was tested during rest in 10 nonathletes and 8 world-class oarsmen. The model states that R = mnR0, where R0 is the intrinsic cardiac rate, and m and n depend only on sympathetic and parasympathetic activity, respectively. The multipliers, m and n, were determined by dual pharmacological blockade in two sessions under similar conditions, but in one session propranolol and in the other atropine was given first. In agreement with the model, when corrections were made for atropine-induced blood pressure changes, m and n did not depend on which blocking agent was administered first. In athletes the control heart rate [55 +/- 3.3 (SD) beats/min] and R0 (81 +/- 8.3 beats/min) were lower than in nonathletes (62 +/- 6.0, P less than 0.01 and 102 +/- 11, P less than 0.001, respectively). The sympathetic multiplier, m, was similar (1.18 +/- 0.06 vs. 1.20 +/- 0.05, P greater than 0.4) in the two groups, but n, the parasympathetic multiplier, was closer to 1 in the athletes (0.57 +/- 0.03 vs. 0.51 +/- 0.05, P less than 0.01). We conclude that the model is suitable for the quantitative study of sympathetic/parasympathetic heart rate control in humans, and that the lower resting heart rate in oarsmen is solely due to a reduction in intrinsic cardiac rate, and not to an increase in parasympathetic tone.
Recovery from central apnea: effect of stimulus duration and end-tidal CO2 partial pressure
Authors: Lawson E. E.
Published: December 2017

The present study was designed to investigate the effect of stimulus duration and chemosensory input on the recovery of central respiratory activity from apnea induced by superior laryngeal nerve (SLN) electrical stimulation. Newborn piglets less than 8 days of age were anesthetized, paralyzed, and mechanically ventilated at differing levels of end-tidal CO2 partial pressure (PCO2). The vagi were cut bilaterally in the neck. Integrated phrenic nerve activity was used as the index of respiratory activity. SLN stimulation caused apnea that persisted after stimulus cessation. The length of apnea following stimulus cessation was directly related to stimulus duration and inversely related to end-tidal PCO2. After apnea, respiratory activity returned gradually to the initial control level. The recovery pattern was well described by a linear regression function using the natural logarithm of time as the independent variable. Prolonging stimulus duration progressively inhibited the amount of initial respiratory activity following apnea. On the other hand, the rate of respiratory recovery was independent of stimulus duration and, except at low end-tidal PCO2 following long (30 s) stimuli, was independent of the end-tidal PCO2 level. These results demonstrate that a long-acting central mechanism regulates recovery from apnea induced by SLN stimulation.
Muscle weakness following dynamic exercise in humans
Authors: Davies C. T. , White M. J.
Published: December 2017

Electrical stimulation of the triceps surae in five healthy male subjects showed that following 1–2 h level running and uphill walking, at submaximal voltages of stimulation, exercise enhanced the twitch and tetanic responses, but the supramaximal time to peak tension (TPT), twitch (Pto) and tetanic tensions (Po) at 10 and 20 Hz were reduced by 16 ms (-12.6%), 11 (-8.9%), 163 (-17.5%), and 230 N (-18.1%), respectively. High-frequency (50 and 100 Hz) tetanic stimulation produced qualitatively similar changes to the 20-Hz response, but the stimulus response curve for the two frequencies was different and the ratio of 20- to 50-Hz response (20/50) (cf. Edwards et al., J. Physiol, London 272: 769–778, 1977) was voltage dependent. The reduction in Po at 100 Hz was associated with a decrease in maximal voluntary contraction (MVC). The effects of exercise on Pto and Po at 10, 20, 50, and 100 Hz were short lived and recovered within approximately 2 h. In contrast box-stepping produced a greater fall in Pto and Po at 10 and 20 Hz, which was long lasting (at least (22 h), and there was a consistent fall in the 20/50 ratio. a 2-min “fatigue” test showed that the muscles were weaker but not more fatigable after exercise. Our results seriously question the validity of using submaximal stimulation voltages and ratios for testing human muscle function and suggest that long-lasting muscle weakness is not associated with recovery from prolonged walking, running, and only observed after box-stepping exercise.
Relationships among lung extravascular fluid compartments with alveolar flooding
Authors: Zumsteg T. A. , Havill A. M. , Gee M. H.
Published: December 2017

We studied the relationship between lung perivascular cuff fluid and alveolar fluid in dogs with alveolar flooding. In one group of dogs, we produced edema with alloxan. We waited 1 h and injected Evans blue dye intravenously. We then caused additional alveolar flooding by a rapid fluid load. The concentration of dye in perivascular fluid cuffs averaged 40% of that in airway edema fluid. We conclude that alveolar fluid derives from microvascular filtrate in the perimicrovascular compartment rather than from fluid in the loose connective tissue spaces. In a second group of dogs, we produced alveolar flooding by mechanically increasing left atrial pressure with a simultaneous fluid load. After flooding stopped and pressures stabilized, we injected Evans blue dye. Morphological examination of lung sections showed no dye present in alveolar fluid, although dye was present in alveolar septa and perivascular cuffs. Flooding occurs during a transient period consistent with an apparent increase in alveolar epithelial permeability, after which an isolated alveolar reservoir is created.
Origin, distribution, and blood flow of bronchial circulation in anesthetized sheep
Authors: Magno M. G. , Fishman A. P.
Published: December 2017

This anatomical-physiological study was undertaken to determine the suitability of the sheep for studies of the bronchial circulation. We designated the terminal portion of the bronchoesophageal artery, which runs to the trachea at the carina, as the “carinal” artery. Postmortem injections of india ink (9 sheep) and Batson's solution (4 sheep) into the carinal artery showed that the carinal artery supplied the bronchi of all lobes except the right apical lobe; the mass of the lung containing bronchi perfused represented 88 +/- 1% of total lung mass. Communications were also found between branches of the carinal artery and branches of the systemic arteries supplying the visceral pleura. In three of six sheep, the carinal artery wedge pressure measured in vivo indicated that patent collaterals were present, but that their incidence is variable. In additional postmortem casts of the aorta made in four sheep after ligation of the carinal artery, the bronchial microcirculation was not entered by the perfusing medium. These data indicate that the collaterals do not contribute significantly to bronchial blood flow and that the carinal artery is the major source of bronchial blood flow in the sheep. In 19 sheep, carinal artery flow, measured electromagnetically, was 0.46 +2- 0.09 ml . min-1 . kg body wt-1. Bronchial blood flow normalized for the weight of the lobes in which bronchi perfused by the carinal artery were located was 3.97 +/- 0.48 ml . min-1 . 100 g lung-1 (n = 11); carinal artery blood flow was 0.39 +/- 0.03% of cardiac output (n = 5). During the 90 min of observation, at normal aortic blood pressure (103 +/- 3.4 Torr), carinal artery blood flow was stable. In conclusion, determination of carinal artery blood flow affords a reliable approach to the bronchial circulation in the sheep.