Decreased exercise hyperpnea in patients with bilateral carotid chemoreceptor resection.

Exercise hyperpnea was compared in 5 asthmatics 25 yr after bilateral carotid body resection (BR), 4 others 19 yr after unilateral resection (UR), and 12 controls (C) matched for age and pulmonary flow limitation. In the BR group, ventilation rose less with exercise, mostly because BR experienced less tachypnea. End-tidal PCO2 rose 5.8 +/- 3.2 (P less than 0.05) to 46 Torr at 50 W. In UR and C the same load did not increase PETCO2 significantly (+2.1 and +1.4 Torr, respectively). Arterial-end-tidal PCO2 differences before and 15--45 s postexercise were insignificant in all three groups. Heart rate and blood pressure rose equally in the three groups, suggesting that the ventilatory effects were not secondary to blood flow differences and disclosing no evidence of baroreceptor denervation during glomectomy.


Lung volume and pleural pressure in the anesthetized hamster.

Lung volumes and respiratory pressures were measured in anesthetized male hamsters weighing an average 117 g. In 16 supine animals functional residual capacity (FRC) determined by body plethysmograph was 1.12 +/- 0.23 (SD) ml (about 20% total lung capacity, TLC) slightly and significantly larger than the FRC measured by saline displacement, 1.01 +/- 0.15 ml. Similar results were found in six prone animals. Paralysis did not significantly alter supine FRC. Contrary to published reports, pleural pressure (Ppl) estimated from esophageal pressure was negative at FRC. The fact that lung volume decreased by 0.2 ml (about 4% TLC) when the chest was opened at FRC provided additional evidence of negative Ppl at FRC. No consistent changes in the lung pressure-volume curve were found after the chest was opened. Deflation chest wall compliance just above FRC was about twice lung compliance. The vital capacity and reserve volumes in this study agreed with values reported in the literature. However, absolute lung volumes (TLC, FRC, and residual volume) were lower by about 1.4 ml, possibly because of earlier overestimates of box FRC.


Regional extravascular lung water in normal sheep.

We measured the regional distribution of pulmonary extravascular water to test our prediction that, because of higher vascular hydrostatic pressure in more dependent zones, the bottom of the lung would tend to be wetter than the top. We injected eight normal sheep under halothane anesthesia with 125I-labeled albumin and killed them 5 min later. We suspended the sheep in the prone position and froze them solid in dry ice. We sawed the thorax into horizontal slices, chipped the frozen lung from each, and determined extravascular lung water and hematocrit. Hematocrit was calculated from separately measured red blood cell (tissue hemoglobin) and plasma (125I-albumin) masses. We found regional extravascular water was constant throughout the lung. Regional hematocrit was significantly higher at the lung base than at the apex in these slowly frozen sheep after death. Calculation of extravascular water using a single blood mass marker (hemoglobin) underestimated lung water, more so at the base than at the apex, because blood mass was overestimated. Accurate measurement of blood mass is critical in the calculation of regional lung water.


Glucose metabolism in rat lung during exposure to hyperbaric O2.

Lung metabolism on exposure to hyperbaric oxygen was studied in rat lungs perfused with artificial media and ventilated with O2 at 0.2, 1, or 5 ATA. During the first 80 min of exposure to O2 at 5 ATA, glucose utilization increased 55%, lactate plus pyruvate production increased 45%, total CO2 production increased 47%, tissue ATP decreased 17%, and the ATP/ADP decreased 29% compared with 0.2 ATA O2. The increased CO2 production was due to a nearly twofold stimulation of pentose cycle activity whereas mitochondrial CO2 production did not change significantly. There were no significant differences in metabolism between lungs studied at 0.2 and 1 ATA O2. During the next hour of perfusion, there was a marked increase in mitochondrial CO2 production of control lungs but tissue ATP/ADP did not change significantly. With oxygen at 5 ATA, mitochondrial CO2 production increased only slightly, tissue ATP/ADP decreased further, and lungs demonstrated accumulation of edema fluid. The results indicate that exposure of lungs to hyperbaric oxygen results in stimulation of NADPH turnover through the pentose cycle and increased ATP generation, although the increased rate was not sufficient to maintain normal ATP/ADP.


Perivascular pressure measurements by wick-catheter technique in isolated dog lobes.

Saline-filled wick catheters were inserted intraparenchymally in the loose connective tissue separating the bronchus and pulmonary artery of unperfused isolated dog lobes. Px, the difference between perivascular pressure and pleural surface pressure (which was atmospheric pressure), was measured by the wick for arterial pressures (Pa) of 10 and 25 cmH2O at lobe transpulmonary pressures (Ptp) of 25, 15, 10, 5, and 2 cmH2O during a deflation pressure-volume maneuver. The response time of Px to step changes in Pa was relatively short, a pressure plateau always occurring in less than 3 min. For Pa of 25 cmH2O, mean Px in five lobes was -2 cmH2O at Ptp of 2 cmH2O and decreased almost linearly to -9 cmH2O at Ptp of 25 cmH2O. Reducing Pa from 25 to 10 cmH2O resulted in a mean decrease in Px of 1 cmH2O at Ptp of 2 cmH2O and 2 cmH2O at Ptp of 25 cmH2O. These results are generally consistent with predictions from a continuum-mechanics analysis of pulmonary vascular interdependence and do not support the concept that perivascular interstitial fluid pressure is different from surface pressure.


A direct-display oscillation method for measurement of respiratory impedance.

The basic principle of the method described here is derived from a variant of the oscillation method. A reference impedance is connected to the mouth; between these two an oscillating flow is imposed. As a reference impedance we use a flexible tube, which acts as a virtually pure inductance or inertance. Respiration is hardly impeded. The only measured parameter is the alternating pressure in front of the mouth and this is easily picked up by a simple microphone. In contrast to former direct-display methods, the inertia and elasticity of the respiratory gas and the respiratory tract, i.e., airways including lungs and thorax, are also taken into account for the evaluation. The respiratory resistance is studied as a complex parameters, i.e., as an impedance. With the aid of diagrams or via electronic computation circuitry, the direct and continuous display of all impedance components such as its magnitude and phase, resistance, and reactance is possible. They can be read out as a function of time, respiratory flow, or volume.


Effects of methacholine and hypocapnia on airways and collateral ventilation in dogs.

We studied the effects of hypocapnia and methacholine on small airways resistance (Rsaw) and collateral ventilation in anesthetized paralyzed dogs. The animals were ventilated with air while either 10% CO2 or air (hypocapnia) was infused through a segment obstructed with a fiber-optic bronchoscope. Measurements were made before and after instillation of methacholine into the obstructed segment. Collateral resistance (Rcoll) and Rsaw increased with hypocapnia and methacholine. The time constant for collateral ventilation increased with hypocapnia, but did not change with methacholine because of decreases in the compliance of the obstructed segment. We conclude that collateral channels respond to methacholine and hypocapnia in a manner similar to small airways and that local parasympathomimetic stimulation, unlike lung deflation does not increase the time constant for collateral ventilation.


Circulatory response to arterial hyperoxia.

We have studied the circulatory response to 100% O2 at 1 and 3 atm, using unanesthetized rabbits in which a systemic artery and the right heart had been cannulated previously. One group of animals served as controls; the other was infused with a flurocarbon emulsion that boosted blood O2 solubility to approximately 5 ml.100 ml-1.atm-1. Exposure to hyperoxia caused an identical sustained rise in arterial PO2 in both groups. O2 uptake was measured during normobaric exposure to 100% O2 and was found to be the same as in control conditions. There was an immediate rise in right heart PO2, more marked in infused animals, but this increase was only temporary, and PO2 dropped, while the right heart-arterial PCO2 difference rose, indicating a gradual fall in cardiac output. This readjustment occurred at a faster rate in the infused animals, a difference that led us to conclude that the peripheral response to hyperoxia is influenced by factors other than arterial PO2. The pronounced decrease in cardiac output seen in infused rabbits was accompanied by lactic acidosis, implying that some of the animals' tissues were becoming hypoxic in the presence of arterial hyperoxia.


Control of respiratory evaporative heat loss in exercising goats.

Investigations were carried out to determine whether a nonthermal input is involved in the control of respiratory evaporative heat loss (REHL) in exercising goats. Two goats were implanted with hypothalamic perfusion thermodes and three goats were implanted with intravascular heat exchangers to clamp hypothalamic temperature and total body core temperature, respectively. At 30 degrees C air temperature REHL was measured while the animals were resting or walking on a treadmill (3 km.h-1, 5 degrees gradient). When the hypothalamic temperature was clamped between 33.0 and 43.0 degrees C the slopes of the responses relating increased REHL to hypothalamic temperature were similar during rest and exercise. However, the threshold hypothalamic temperatures for the increased REHL responses were lower during exercise than at rest, presumably due to higher extrahypothalamic temperatures. When the body core temperature was clamped between 37.0 and 40.4 degrees C the slopes of the responses relating increased REHL to total body core temperature during exercise showed only minor differences compared to those at rest, none of them conclusively indicating nonthermal influences.


Effect of static or slowly flowing blood on carbon monoxide diffusion in dog lungs.

During temporary left pulmonary artery occlusion (TLPAO) in dogs, blood in pulmonary capillaries downstream from the occlusion is static or flowing slowly. In such areas, the uptake of carbon monoxide (CO) and diffusing capacity (DLCO) should decrease with time as carboxyhemoglobin concentration increases. We measured DLCO during exhalation of five sequential breaths in anesthetized dogs using a modification of a technique recently described in our laboratory (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 43: 617--625, 1977). During TLPAO, the decrease in DLCO was greatest at low lung volumes, suggesting that the occluded lung was emptying later in exhalation, a conclusion supported by measurements of DLCO during TLPAO with the right mainstem bronchus occluded. In addition. DLCO decreased with each breath as the backpressure to diffusion increased in static capillary blood. Inhalation of 4% CO accelerated the rate of decrease in DLCO. Measurement of DLCO during exhalation over multiple breaths may help detect pulmonary vascular obstruction.


Stimulation of phrenic nerve activity by salicylate.

To assess the possibility that salicylate stimulates VE by direct excitation of phrenic motoneurons, we compared two groups of anesthetized vagotomized dogs with respect to increases in phrenic nerve activity elicited by a large dose of sodium salicylate (225 mg/kg). The sole difference between the two groups of animals was the condition of the spinal cord (SC); SC remained intact in one group of animals (i.e., intact animals) whereas the other group of animals (i.e., T1 spinal-transected animals) underwent complete transection of the SC at the first thoracic level. Both groups of animals were ventilated by a respirator and arterial PCO2 was maintained constant throughout all experiments. Following salicylate infusion, intact animals exhibited two- to threefold increases in the frequency of phrenic nerve bursts and three- to fivefold increases in moving average minute phrenic activity (i.e., the summation of peak integrated burst activity per minute). In contrast, salicylate infusion into T1 spinal-transected animals elicited no statistically significant increase in the frequency of phrenic nerve bursts while increases in minute phrenic activity were limited to 32 +/- 8%. Since T1 spinal transection markedly diminishes increases in phrenic nerve activity elicited by salicylate, we conclude that salicylate stimulates VE by a reflex mechanism whose afferent pathways originate in metameres below T1.


Anaerobic threshold alterations caused by endurance training in middle-aged men.

Nine previously sedentary middle-aged males underwent cycle endurance training 45 min/day for 9 wk with an average attendance of 4.1 days/wk. Seven males served as controls. Before and after the training period, the subjects performed three cycle ergometer tests. Work rate was incremented by 15 W/min, to the limit of the subjects' tolerance, in the first two tests; the third test consisted of contant-load cycling at an O2 uptake (VO2) just below the pretraining anaerobic threshold (AT). After training, the AT increased significantly by 44%, expressed as absolute VO2, and by 15%, expressed relative to VO2 max. Significant increases were also noted in VO2max (25%), maximal minute ventilation (19%), and maximal work rate (28%). The test-retest correlation coefficients for the AT (%VO2max) were 0.91, pre- and posttraining. Training did not alter steady-state VO2 during the submaximal exercise test whereas significant decreases occurred in CO2 output, VE, respiratory quotient, and VE/VO2. No changes occurred in the control subjects during this period. These results demonstrate that the AT is profoundly influenced by endurance training in previously sedentary middle-aged males.


Mechanism of decreased blood flow to atelectatic lung.

This study examined the relative contribution of passive mechanical forces vs. hypoxic pulmonary vasoconstriction as mechanisms of blood flow reduction through atelectatic canine lung. Selective atelectasis of the left lower lobe caused the electromagnetically measured lobar blood flow to decrease 59% from control levels. Reexpansion and ventilation of the left lower lobe with 95% N2-5% CO2, which should terminate any passive mechanical contribution to the decreased test lobe blood flow, did not cause any significant increase in left lower lobe blood flow. Ventilation of the left lower lobe with 100% O2, which should terminate any hypoxic pulmonary vasoconstriction contribution to the decreased test lobe blood flow, increased blood flow back to levels not significantly different from control. Differences between degree of hypoxia, magnitude of transpulmonary pressure, and absolute pulmonary vascular pressure during left lower lobe atelectasis and ventilation with N2 were considered to be minor influences. I conclude that the mechanism of decreased blood flow to an atelectatic lobe is hypoxic pulmonary vasoconstriction.


Thermoregulation in unrestrained rats during and after exposure to 1.5--4 G.

Unrestrained rats were exposed to cold for 1 h during and immediately after exposure to hypergravic fields (1.5--4 G) to determine if they recover their ability to thermoregulate on reentry to 1-G conditions. In contrast to the decreased body temperatures observed when cold exposure occurred concurrently with acceleration, hypothalamic, carotid, and brown fat temperatures did not fall when rats were exposed to cold immediately after return to 1 G. These results support the hypothesis that the thermoregulatory alterations seen under hypergravic conditions are manifestations of an effect of ongoing exposure to hypergravity and can be reversed on termination of acceleration. The reversibility of the thermoregulatory impairment is apparently unaffected by the magnitude of the acceleration field over a range of 1.5--4 G.


Determinants of gas exchange kinetics during exercise in the dog.

Following exercise onset, CO2 output (VCO2) and O2 uptake (VO2) increase exponentially, but with appreciably different time constants. To determine the sensitivity of the time courses of these variables to altered ventilatory kinetics, rhythmic exercise was induced abruptly in anesthetized dogs by bilateral stimulation of the peripheral ends of the cut sciatic and femoral nerves. This increased the metabolic rate by 83 +/- 25 (SD) %. The dogs were ventilated with a constant-volume pump, the frequency of which was changed exponentially from the start of the exercise up to the ventilation that returned arterial CO2 and O2 pressure (PCO2 and PO2) in the steady state to resting levels. The time constant (tau) of  the increase in ventilation (VE) was varied among trials. VCO2, VO2, end-tidal PCO2 and PO2, and arterial PCO2 were measured breath by breath. tauVO2 was constant at approximately 18 s regardless of alterations in tauVE. In contrast, tauVCO2 was strongly dependent on tauVE, apparently due to the larger body stores for CO2; the transitions were isocapnic when tau VE was approximately 40 s. We conclude that ventilatory dynamics can markedly influence the dynamics of CO2 exchange during exercise, but has no appreciable effect on O2 uptake dynamics.


Thermal increment provided by inhalation rewarming from hypothermia.

To quantify the core temperature gain derived from inhalation rewarming, 10 subjects were immersed in seawater (mean temperature 12 degrees C) until a 2 degree C drop in rectal temperature occurred, and were then rewarmed by breathing hot saturated air at 45 degrees C for 30 min. Each subject was rewarmed once breathing air and once rebreathing a controlled fraction of expired air adjusted to produce a hyperventilation of 50 l/min. After 30 min of rewarming mean rectal temperature had increased 0.39 degrees C in subjects breathing air compared with 0.77 degrees C in those hyperventilating (P less than 0.01). Corresponding gains in tympanic temperatures were 1.1 and 1.5 degrees C, respectively. Calculations indicate that the additional heat input with hyperventilation yielded a core (rectal) temperature gain of 5.1 X 10(-4) degrees C/l. It is concluded that each additional 10 l/min of ventilation of hot saturated air will increase the rate of core rewarming from hypothermia by approximately 0.3 degrees C/h.


Metabolic and cardiopulmonary responses to wheelchair and bicycle ergometry.

To evaluate wheelchair activity in reference to a more familiar mode of locomotion, metabolic and cardiopulmonary responses to wheelchair ergometer (WERG) and bicycle ergometer (BERG) exercise were compared. Eighteen able-bodies subjects were tested on a combination wheelchair-bicycle ergometer. Oxygen uptake (VO2), respiratory exchange ratio (R), pulmonary ventilation (VE), ventilatory equivalent (VE/VO2), percent net mechanical efficiency (ME), and heart rate (HR) were determined at power output (PO) levels of 30, 90, and 150 kpm/min on each ergometer. For WERG and BERG exercise, VO2, VE, and HR increased linearly with PO. Generally, VO2, R, VE, VE/VO2, and HR responses were higher (P less than 0.05) during WERG than BERG exercise at each PO. Blood lactate was determined after 150 kpm/min, and found to be higher (P less than 0.05) during WERG than BERG exercise. ME increased with PO and was lower (P less than 0.05) for WERG than BERG exercise at each PO level. The greater metabolic and cardiopulmonary responses observed during WERG exercise may be due to inefficient biomechanics and the relatively small upper body musculature used for propulsion.


Rib cage deformation during static inspiratory efforts.

Patterns of rib cage (RC) deformation were studied in six normal subjects during moderate static inspiratory efforts such that esophageal pressure (Pes) as an index of transthoracic pressure fell to between -30 and -60 cmH2O during each maneuver. At lung volumes below 50% inspiratory capacity (IC), static inspiratory efforts deformed RC to a more elliptical shape; RC lateral diameter became smaller and RC lateral diameter became larger. However, at high lung volumes (greater than 50% IC) the opposite change in RC dimensions occurred despite similar changes in Pes, i.e., the RC became more circular. These differences in RC deformation did not appear to be a possive consequence of increased lung volume because the RC could be voluntarily deformed to a more circular shape at low lung volume when a) subjects performed static inspiratory efforts mainly with their intercostal and accessory muscles rather than their diaphragm as judged by a smaller change in transdiaphragmatic pressure for the same Pes; or b) subjects statically contracted their diaphragm with it held in a relatively flattened configuration as assessed by a large abdominal AP dimension. We suggest that deformation of the RC during static inspiratory efforts is not as predictable as has previously been suggested but depends on the pattern of contraction and configuration of the respiratory muscles.


Breathing pattern and ventilatory response to carbon dioxide in divers.

The breathing pattern and ventilatory response to carbon dioxide of 10 experienced divers was compared with that of 10 nondivers of similar age and build. Breathing pattern was described by the equation VE = M (VT - K) and the response to carbon dioxide by VE = S(PCO2 - B). The divers exhibited a value form 27% lower than the nondivers; S was 33% lower. The difference was significant (P less than 0.05) in both cases. B was significantly higher (P less than 0.05) in the divers than nondivers. These differences are not attributable to age, build, or vital capacity. S was well correlated with M when all subjects were considered a single group. Within the diving group no correlation of S and M with diving experience was found.


Thermoregulation in swimmers and runners.

Thermoregulatory responses of six trained swimmers and five runners to cold and heat were evaluated during 30 min of exercise (60% VO2max) while immersed to the neck in 20, 25, 30, and 35 degrees C water. Mean oxygen uptake was similar for both groups during all four trials. Changes in metabolic rate during the 8th to 28th min were significantly greater for the runners in 20 degrees C water, and swimmers in 30 and 35 degrees C water. Heart rates, Tsk, delta Tre, Tb, body heat content, and heat storage were dependent on water temperature. Runners were able to attain higher sweat rates than swimmers in 35 degrees C water. Swimmers had significantly greater tissue conductance values in the 35 degrees C exposure. Swimmers thermoregulated better in 20 degrees C water than runners, possibly due to a larger surface area-to-volume ratio, percentage body fat, subcutaneous fat, or improved vasomotor control. Exercise in the heat was better tolerated by runners. Physical training in water does not improve heat acclimatization to the extent of training in air, but does improve cold tolerance.


Effects of training on postexercise limb muscle EMG synchronous to respiration.

Twenty university students (10 trained and 10 untrained) participated in 60 sessions testing the effect of training on postexercise electromyogram synchronous to respiration. The latter was recorded for m. biceps brachii dextra, m. quadriceps femoris dextra, and m. gastrocnemium dextra. The respiration rate was taken before and after three levels of functional effort performed on a bicycle ergometer. The first (2 X 30 s with a 20-s interval at 100 rpm and 245 W) and the second (5 X 1 min with a 30-s interval after each min, at 90 rpm and 200 W) were of speed-developing nature; the third (20 min at 60 rpm and 117 W with 1-min interval every 5 min) was to develop endurance. Our observations show that the greatest percentage of a synchronous-to-respiration muscle bioelectric activity can be observed after the first two types of effort. In the third type the percentage is smaller and the duration of the activity is shorter. On the other hand, the percentage of biopotential occurrence is greater for untrained persons, with a considerable longer disappearance time. The phenomenon can be used as a criterion in the athlete's functional diagnosis.


Comparison of phrenic motoneuron responses to hypercapnia and isocapnic hypoxia.

This study was undertaken to compare phrenic motoneuron responses to hypercapnia and isocapnic hypoxia. Efferent activity of single phrenic nerve fibers was recorded with that of the contralateral phrenic nerve in decerebrate cats which were vagotomized, paralyzed, and artificially ventilated. At normocapnia in hyperoxia, single phrenic fibers were distributed into approximately equal "early" and "late" populations according to their onset of activity relative to the period of the phrenic burst. Elevations of PACO2 or diminutions of PAO2 resulted in progressive increases in the number of spikes per respiratory cycle and decreases in the modal interspike interval for both early and late units. Moreover, either stimulus caused an onset of late unit activity at progressively earlier portions of inspiration. At equivalent levels of peak integrated phrenic discharge achieved at normocapnia or hypercapnia as compared to normoxia or hypoxia, there were no differences in activity patterns for either early or late units. It is concluded that hypoxia-induced alterations in the activity of single phrenic motoneurons are identical to those changes resulting from hypercapnia.


Effects of inspiratory flow pattern on gas exchange in normal and abnormal lungs.

To study the influence of inspiratory flow pattern on gas exchange in normal and abnormal lungs, 15 dogs were mechanically ventilated with the ascending or descending half of a rectified sine-wave flow pattern during pentobarbital anesthesia. Blood-gas status and cardiac output were monitored during each pattern. Pulmonary injury was induced in 9 animals by prior injection of oleic acid into the right atrium. Ventilation was with room air and zero end-expiratory pressure. Although no significant difference was seen between the patterns in animals with normal lung function (PaO2 greater than 85 Torr on the ascending pattern), the descending pattern resulted in a rise in PaO2 of about 10% (P less than 0.01) in animals with abnormal lung function (PaO2 less than 70 Torr on the ascending pattern). No significant difference in PaCO2 or cardiac output was detected when flow pattern was changed in any of the animals. We conclude that inspiratory flow pattern is not a significant factor when ventilating normal lungs, but may improve gas exchange significantly when severe ventilation-perfusion maldistributions exist.


Mechanism of rapid, shallow breathing after ozone exposure in conscious dogs.

In 10 experiments on 3 conscious dogs exercising on a treadmill, we studied the effect of ozone on base-line ventilation and on ventilatory responses to inhaled bronchoconstrictor drugs. Prior to ozone exposure, inhalation of histamine diphosphate aerosol (1%; 5 breaths) increased respiratory frequency (f) by 86 +/- 11% (mean +/- SE), and inhalation of prostaglandin F2 alpha (PGF2 alpha) aerosol (0.1%; 5 breaths) increased f by 74 +/- 16%. Immediately after ozone exposure %0.65 ppm; 2 h), steady-state base line f was increased by 120 +/- 18% and tidal volume (VT) was decreased by 43 +/- 5%. When conduction in the cervical vagus nerves (that were exteriorized permanently in skin loops) was blocked by cooling, these changes caused by ozone were abolished (P greater than 0.05). The increased responses to both histamine and PGF2 alpha aerosols after ozone were unaffected by pretreatment of isoproterenol aerosol (0.5%; 15 breaths), but were completely abolished by vagal cooling. Our studies indicate that ozone-induced rapid, shallow breathing and the increased ventilatory responses to inhaled histamine and PGF2 alpha aerosols are mediated through vagal afferent pathways.


Effect of hyperoxia on oxygen consumption in exercising ponies.

Published reports of oxygen consumption (VO2) during exercise in hyperoxia are equivocal. By and large, when measured at the lung using respiratory gas equations, VO2 is elevated in hyperoxia and, when measured at the blood-tissue level using the cardiovascular Fick (CVF) equation, it is unchanged. We sought to provide some insight into this problem by making through the use of both equations simultaneous determinations of VO2 during hyperoxia in exercising ponies. In normoxia, during treadmill exercise (115 m/min, 10% grade) of seven ponies, there was no difference in exercise VO2, whether it was measured by the Haldane transformation (HT) or CVF equations (P greater than 0.05). In hyperoxia, the exercise VO2 was significantly increased from the normoxia condition (P less than 0.05) when measured by the HT equation but not when measured by the CVF equation (P greater than 0.05). By use of the CVF equation as the method of choice for VO2 determinations in hyperoxia, the present data show no change in exercise VO2 in the hyperoxic condition.


Acceleration forces at eye level experienced with rotation on the horizontal bar.

Negative acceleration forces (-Gz) experienced at eye level have been associated with preretinal hemorrhage and headache. These signs and symptoms were found in individuals who experienced negative (toward the head) force while rotating on a horizontal bar or hanging from a trapeze. Lightweight accelerometers were used to measure -Gz experienced at eye level in children and adult gymnasts performing a single-knee backswing on a horizontal bar. Rate of onset of -Gz, peak -Gz, time experiencing -Gz, area of curve (G.second), and mean force (area/time) were calculated. There was no significant difference between the children and the adult gymnasts in any of the above parameters. The best gymnast had a maximum rate of onset of 38.15 G/s and the maximum negative force experienced was 5.52 G. The maximum rate of onset for a child was 41.56 G/s and the maximum negative force experienced was 5.73 G. Compared with -Gz tolerance curves generated on a centrifuge the best gymnast would have become symptomatic while performing this maneuver in 6 s. The best child would have become symptomatic in 25 s. These tolerance limits can be easily exceeded by gymnasts and by the monkey-bar enthusiast.


Breath-by-breath variation of FRC: effect on VO2 and VCO2 measured at the mouth.

We examined breath-by-breath (B-B) variations of FRC (delta FRC) and their effect on measured O2 and CO2 gas exchange in 52 2- to 4-min segments of continuous air breathing obtained in 29 patients (age range 6--50 yr). Respiratory frequency ranged from 13 to 43 breaths/min, VE from 6.7 to 22.5 l/min (BTPS), and expired VT from 234 to 1,370 ml (BTPS). Computer analysis was based on the following source data measured at the mouth: inspired (VI) and expired (VE) gas flow, FN2, FO2 and FCO2. The analysis provides B-B evaluation of VI, VE, delta FRC in terms of VN2, and VO2 and VCO2 at the mouth and at the alveolar level, i.e., after correction for delta FRC. Significant B-B variations of FRC were found in all studies. delta FRC ranged from +360 to -360 ml (BTPS). For single respiratory cycles VI - VE is primarily a function of N2 exchange at the mouth (VMN2). VO2 and VCO2, uncorrected for delta FRC, are significantly more dispersed about mean values than the corrected gas uptakes (P less than 0.0005). The data support the view that the assumption of VIN2 = VEN2 is invalid for single respiratory cycles. Determination of breath-by-breath VO2 and VCO2 should therefore, not be based on steady-state gas uptake equations. It requires measurement of both inspired and expired breath volumes and evaluation of N2 gas exchange.


Effects of carotid body denervation on respiratory pattern of awake cats.

Eight awake cats have been studied before and after carotid denervation during air and oxygen breathing, and during hypercapnia. Analysis of the variables that characterize the spirogram shows that carotid denervation consistently results in a decrease of the mean inspiratory flow (VT/TI), causing a decrease in tidal volume (VT) and ventilation with a relative alveolar hypercapnia. In carotid-denervated animals, inhalation of oxygen results in an increase in ventilation due to an augmentation of VT/TI and VT and a relative hypocapnia. TI does not significantly change in the different conditions whereas TE is significantly affected. TE seems therefore to be more closely related to the rate of rise of inspiratory activity than to inspiratory duration.


One- and three-minute exercise response in coronary artery disease.

Treadmill exercise responses of oxygen uptake (VO2), CO2 production (VCO2), and venoarterial CO2 difference (Cv-Ca), measured by CO2 rebreathing (Defares technique) at 1 and 3 min of exercise, were studied in two separate series of control (apparently healthy) and coronary artery disease (CAD) subjects. In the 1-min series there were 21 controls and 15 CAD subjects. In the 3-min series there were 21 controls and 18 CAD subjects. All were males, ages 30--60 yr, and the CAD subjects had histories of myocardial infarction. In both series VO2 at 1 min and power requirement (P ) = 1,000 (VO2-1-1,000) was estimated where P =weight (kg) X grade (fractional) X walking speed (m/min). In the 1-min series (P = 1,000) all measurements were made at 45--60 s in separate test runs. In the 3-min series P was 750 kg.m/min, VCO2 and VO2 were measured at 2.5--3 min exercise, and Cv-Ca was measured at 3--3.25 min in the same test run. Data indicate that the average cardiac output (Q) for control subjects was 15 l/min in both series with lower values for CAD subjects. At 1 min reduced Q was accompanied by reduced VO2 or VCO2 and increased Cv-Ca, whereas at 3 min reduced Q was accompanied by increased Cv-Ca.


Respiratory response to HCl acidosis in dogs after carotid body denervation.

To test the participation of the carotid bodies in the respiratory response to metabolic acidosis, six dogs were infused with HCl for 2 h followed by HCl feeding to prolong the acidosis to 48 h. This protocol was repeated after carotid body denervation (CBD). Mean control PCO2 rose by 7.3 Torr after CBD. PCO2 fell comparably during acidosis before and after CBD at all time periods from 30 to 48 h and returned to control levels by 72 h. The pH ranged from 7.10 to 7.30 during acidosis pre- and post-CBD. The decreases in pH and bicarbonate concentration did not differ significantly at any time interval between the pre- and post-CBD studies. This study indicates that in dogs moderately severe HCl acidosis stimulates ventilation acutely and chronically through a central mechanism in the absence of the carotid bodies.


Abolition of a viscerosomatic reflex during oxygen deprivation.

Effect of hypoxia was studied on the J reflex, a term used for the reflex inhibition of muscular exercise by activation of type J pulmonary endings. Hypoxia was induced by ventilating the animal with gas mixtures varying from 18 to 9% oxygen in nitrogen. The blood gas tensions of the arterial blood (PaO2) were measured before, during, and after hypoxia. It was found that the J reflex is sensitive to a reduction in oxygen. A fall in PaO2 between 67 and 47 Torr abolished this reflex. Studies were also undertaken to exclude the possibility that the effect of hypoxia was predominantly exerted on monosynaptic reflex itself. A similar fall in PaO2 also depressed the monosynaptic reflex. Minimum time required for the significant depression was 32 s. On the contrary the J reflex was abolished within this period suggesting that the abolition of J reflex is independent of the changes in monosynaptic reflex during hypoxia.


Cerebral gas exchange: perfusion and diffusion limitations.

The simultaneous washout of argon and methane from brain tissue stores was studied in anesthetized dogs that were rendered either hypocapnic or hypercapnic. The washout pattern can be analyzed in terms of two compartments with different rate constants. The two tracers were eliminated at the same rate from any one compartment in either experimental condition. Because argon and methane have the same blood-brain partition coefficient, and a ratio of molecular weights of 2.5, we conclude that their transport into or from the brain is not limited by diffusion over a wide range of cerebral blood flows.


Hypopnea consequent to reduced pulmonary blood flow in the dog.

The ventilatory responses to diminished pulmonary blood flow (Qc), as a result of partial cardiopulmonary bypass (PCB), were studied in chloralose-urethan-anesthetized dogs. Qc was reduced by diverting vena caval blood through a membrane gas exchanger and returning it to the ascending aorta. PCB flows of 400--1,600 ml/min were utilized for durations of 2--3 min. Decreasing Qc, while maintaining systemic arterial blood gases and perfusion, results in a significant (P less than 0.05) decrease in expiratory ventilation (VE) (15.9%) and alveolar ventilation (VA) (31.0%). The ventilatory decreases demonstrated for this intact group persist after bilateral cervical vagotomy (Vx), carotid body and carotid sinus denervation (Cx), and combined Vx and Cx. The changes in VE and VA were significantly (P less than 0.001) correlated with VCO2 changes, r = 0.80 and r = 0.93, respectively. These ventilatory changes were associated with an overall average decrease in left ventricular PCO2 of 2.1 Torr; this decrease was significant (P less than 0.05) only in the intact and Cx groups. Decreasing pulmonary blood flow results in a decrease in ventilation that may be CO2 related; however, the exact mechanism remains obscure but must have a component that is independent of vagally mediated cardiac and pulmonary afferents and peripheral baroreceptor and chemoreceptor afferents.


Real-time moment analysis of pulmonary nitrogen washout.

A real-time moment analysis was applied to multibreath nitrogen-washout dynamics of the lung. Because the analysis accounts for breathing pattern variations, subjects could perform the washout with spontaneous breathing. The real-time digital processing of the nitrogen and flow signals incorporates filtering, delay compensation, and corrections for the effects of gas composition and temperature changes. In our study, moment analysis of the multibreath washout was evaluated for 37 subjects: 6 normal nonsmokers, 4 "normal" smokers, 6 asthmatics, 12 with diffuse interstitial disease, and 9 with chronic obstructive pulmonary disease. Moments were computed from end-tidal and breath-averaged nitrogen fractions. The ratio of 1st-to-0th moments was found to yield distinctions among subjects with different degrees of ventilation inhomogeneity, even between normal nonsmokers and "normal" smokers. With minimal computational facilities, this moment analysis not only provides a sensitive index of ventilatory dysfunction, but also a cost-effective tool.


Transient response of the Geman-Miller respiratory oscillator model.

Recent evidence suggests that there is a persistence of elevated respiratory center activity for many respiratory cycles after the cessation of a neural stimulus. To explore the theoretical possibility that this behavior may be a consequence of the neural oscillator that dictates respiratory rhythm, the transient response of a mathematical model of a medullary respiratory oscillator recently described by Geman and Miller was examined using computer simulation. This concept was motivated by the presence of a persistent transient response behavior inherent in oscillators from mathematical physics. The results indicate that a transient persistence effect is evident in the model behavior under some conditions, and this effect as well as the steady-state amplitude is markedly sensitive to the shape of the saturation function that interconnects the neuron populations. Furthermore, this behavior is initiated by either an abrupt decrease in a tonic input or an abrupt decrease in the synaptic weights connecting subpopulations of neurons.


A dryer for rapid response on-line expired gas measurements.

A dryer is described for use in on-line breath-by-breath gas analysis systems. The dryer continuously removes water vapor by condensation and controls the sample gas at 2 degrees C dew-point temperature or 5 Torr water vapor partial pressure. It is designed to operate at gas sampling flow rates from 0.5 to 1 1.min-1. The step-response time for the described system including a Beckman LB-2 CO2 analyzer, sampling tubing, and dryer is 120 ms at 1 l.min-1. The time required for gas samples to transport through the dryer is 105 ms at a gas sampling-flow rate of 1 l.min=1.


A method for measurement of oxygen uptake in neonates.

The frequent use of continuous positive airway pressure and positive end-expiratory pressure in newborn infants with pulmonary disease has prevented the use of conventional methods for measuring oxygen uptake (VO2) in intensive-care units. A feed-back replenishment technique for the determination of the oxygen uptake of these newborn infants has been developed. An instrument utilizing this method has been designed and built permitting continuous VO2 monitoring without interfering in the routine ventilatory therapy of the critically ill infant. Theoretical, bench, and animal experiments using room air as an inspired gas indicate instrument accuracies as a percentage of full scale of 2.4, 2.8, and 7.3, respectively. Preliminary trials on infants demonstrate that the instrument functions satisfactorily in the newborn intensive-care unit.


Concurrent exercise of dogs using carousel-type treadmill.

To exercise several animals at the same time, a carousel-type treadmill was constructed. Horizontal extensions secured to a motorized central shaft allow six dogs to be run concurrently. To counter the effect of centrifugal force, a rubberized banked running track was built. The track was also designed so that it can be hosed down for easy maintenance. During the past 2 yr, the treadmill has not required any maintenance, and only minimal attention has been necessary on the track.


Temperature regulation and hypohydration: a singular view.

Body temperatures of exercising humans who have been denied water are elevated when compared to hydrated controls. The simplest "explanation" for the elevated temperature is a decrease in sensitivity of the sweating mechanism. This and similar "explanations" do not direct attention to basic causes but only the result(s) of more fundamental aspects of regulatory physiology. Among the items considered in this speculative presentation are influences of changes in osmolarity, specific ions, peptide hormones, fluid shifts, and muscular contractions during exercise. A hypothesis is offered for consideration in explaining elevations of body temperature in exercise with and without water replacement. In general, the hypothesis relates changes in hypothalamic osmotic pressure and/or ionic constituents with fluid and ionic events in muscle during exercise. The fluid and ionic shifts are probably proportional to the amount of lean body mass engaged in dynamic exercise. Since blood volume has also been shown to be related to lean body mass, similar relative work loads should lead to similar changes in the osmotic and/or ionic environment of the hypothalamus, thus resulting in similar increases in body temperature during exercise. Hypohydration is superimposed on this basic response. Increases in body temperature of resting hypohydrated subjects appear to be due to increases in osmotic pressure and/or specific ion concentrations. During exercise, these changes are added to those induced by muscle contraction. The focal point of all such ionic and osmotic changes is thought to be neural processes within the hypothalamus.


Effects of graded reduction of brain blood flow on ventilation in unanesthetized goats.

The ventilatory effects of graded reductions in brain bloow flow (BBF) were studied in unanesthetized goats. At a BBF of 85% of control (PVO2 = 29.2 Torr, PVCO2 = 47.3 Torr) there were no clear ventilatory effects. At BBF of 70% of control (PVO2 = 25.2, PVCO2 = 50.5) and 50% of control (PVCO2 = 22.3, PVCO2 = 53.0) there was hyperpnea, due primarily to an increase of tidal volume. Further reduction of BBF (avg of 42% of control) first produced intense tachypnea and then (30--40% of control) caused apnea that was reversible. At 50% BBF there was a reduction of brain O2 consumption, (4.67--4.00 ml/min) and an increase in systemic O2 consumption. beta-Adrenergic blockade prevented the increase in systemic O2 consumption and reduced the hyperpnea by two-thirds at 50% BBF; the residual hyperpnea was associated with hypocapnia in contrast to the hyperpnea prior to beta-adrenergic blockade, which was virtually isocapnic. The data suggest that hyperpnea due to brain ischemia is a result of both brain acidosis and systemic hypermetabolism. The similarity of the pattern of responses to that previously reported for progressive carboxyhemoglobinemia suggests that brain hypoxia is a determinant of the ventilatory responses to brain ischemia.


Effects of morphine on ventilatory response to exercise.

The effects of analgesic doses of morphine on ventilation, arterial blood gas tensions, chemical control of breathing, and the ventilatory response to exercise were studied in six normal subjects. After administration of 0.2 mg/kg morphine, resting ventilation decreased primarily because of a reduction of tidal volume. Ventilatory responses to carbon dioxide and hypoxia were significantly reduced to one-half and one-third of control, respectively. Ventilatory responses at any given level of exercise were significantly reduced after morphine. However, since oxygen consumption during exercise was similarly reduced after morphine, the relationship between ventilation and metabolic rate during steady-state exercise was not altered by the drug. In addition, morphine prolonged the attainment of steady-state ventilation in four of the six subjects, similar to that reported for chemodenervated subjects. The findings suggest that blunting of chemoreception for hypoxia and hypercapnia has no effect upon the link between metabolic rate and ventilation during steady-state exercise, but the hypoxia chemoreflex may be involved in determining the dynamic characteristics of the response.


Ventilatory response to muscular exercise: observations regarding a humoral pathway.

To assess the role of humoral mechanisms in eliciting the hyperpnea of muscular exercise, anesthetized dogs underwent complete spinal transection at the second lumbar level (L2). Muscular exercise of the denervated hindlimbs was then induced by electrical stimulation. Coincident with hindlimb muscle contraction, oxygen consumption (VO2) increased 173% and ventilation (VE) increased 163%; no statistically significant changes occurred in arterial carbon dioxide tension (PCO2), arterial pH, or arterial oxygen saturation. Similar results were obtained after peripheral chemodenervation and vagotomy plus spinal transection. In order to evaluate the possibility that extracranial receptors mediate the increases in VE elicited by exercise-induced humoral factors, heads of vagotomized L2 spinal-transected dogs were perfused entirely by a support dog with blood of unchanging gas composition via both carotid and both vertebral arteries. The carotid bodies lay within the region of the perfused head; the aortic bodies were denervated. These L2 spinal-transected head-perfused animals still responded to hindlimb exercise with a 156% increase in VO2 and a 122% increase in VE. We conclude that muscular exercise can stimulate VE via humoral factors other than usual chemical stimuli in arterial blood (i.e., PCO2, pH, or O2 saturation). Extracranial receptors (other than conventional peripheral arterial chemoreceptors) appear to mediate a major portion of the increase in VE elicited by exercise-induced humoral factors.


Vagal effects on histamine, carbachol, and prostaglandin F2 alpha responsiveness in the dog.

To investigate whether an individual dog's responsiveness to histamine correlates with its responsiveness to other bronchoconstrictor agents and to investigate whether varying vagal effects account for the previously described range of histamine responsiveness, we compared dose-effect relationships of histamine to those of two pharmacological dissimilar agents, carbachol and prostaglandin F2 alpha before and after vagal blockade. There was a highly significant correlation between histamine and both carbachol (P less than 0.001) and prostaglandin F2 alpha (P less than 0.001) responsiveness. The range of responsiveness to prostaglandin F2 alpha was greater than that for histamine or carbachol. When histamine and carbachol were given simultaneously, a purely additive effect was found. Vagal blockade had no significant effect on histamine or carbachol responsiveness, but significantly diminished the responsiveness to prostaglandin F2 alpha; however, it neither narrowed the range nor changed the rank order of responsiveness. We conclude that the range of responsiveness is not specific for any one agent and that vagal mechanisms do not play a role in producing this range.


Hemodynamic responses of dog lung lobe to lobar venous occlusion.

We perfused the left lower lobe of the dog lung with constant flow. When the lobar venous outflow was occluded, the lobar venous pressure rose suddenly to a level somewhere below the arterial pressure, and then the arterial and venous pressures began to rise more slowly. A possible explanation for this response is that, when the outflow was occluded, flow through some downstream segment of the bed ceased. Because flow into the lung continued, the arteriovenous pressure difference after occlusion represents the pressure drop across some upstream segment through which the flow continued. We designated the arteriovenous pressure difference just after outflow occlusion as the upstream pressure drop. The arteriovenous pressure difference before occlusion minus the upstream pressure drop was designated the downstream pressure drop. In an attempt to better understand the meaning of the upstream and downstream pressure drops, we examined the influence of pulmonary vasoconstriction and flow direction on the size of the upstream and downstream pressure drops. We also compared these pressure drops with the pressure drops occurring upstream and downstream from the midpoint of the lobar vascular volume, using the low-viscosity bolus technique. The results indicate that changes in the upstream and downstream pressure drops, as evaluated by outflow occlusion, reflect changes in the lobar arterial and venous resistances.


Adrenal component to pulmonary hypertension induced by elevated cerebrospinal fluid pressure.

In this study we investigated the possibility that a circulating vasoactive agent contributes to the pulmonary hypertension elicited by elevated cerebrospinal fluid pressure (PCSF) using a denervated canine left lower lung lobe (LLL) preparation that was pump perfused with mixed venous blood at constant flow and venous pressure. Raising the PCSF to an average 190 Torr resulted in a 34.3% increase in LLL inflow pressure. This response was eliminated by adrenal venous occlusion and also by alpha-blockade of the LLL. The results indicated that adrenal catecholamines were responsible for the LLL response. The passively induced elevation of left atrial pressure (Pla) that occurs in the intact animal during elevated PCSF was stimulated in the LLL by raising the outflow pressure. This maneuver attenuated the increase in LLL vascular resistance and suggested that the elevation in Pla seen in the intact animal could mask humorally mediated responses of the magnitude we observed.


Human pulmonary resistance: effect of frequency and gas physical properties.

We have investigated a new technique that could be specific for detecting small airway diseases. We measured resistance in nine subjects, evaluating the effect of breathing 80% He-20%O2, air, and 80% SF6-20% O2 at different flow rates (0.25--1.01 l/s) and frequencies (4--12 Hz). To test the sensitivity and specificity of this new technique, we used intravenous histamine infusion to cause peripheral constriction. During histamine infusion six of nine subjects showed the following changes: 1) dynamic compliance decreased; 2) subjects developed frequency dependence of compliance, and 3) there was no significant change in pulmonary resistance or Rrs (respiratory resistance) at 4 Hz. These data suggested a time-constant discrepancy in the periphery due to histamine infusion. These six subjects also developed frequency dependence of resistance (delta Rrs from 4 to 12 Hz), which was significant when breathing air (-22 +/- 6%) and maximal when we used He-O2 (-32 +/- 3%). We conclude that He-O2 can improve the specificity of frequency dependence of Rrs for detecting events occurring in the peripheral airways.


Respiratory impedance and derived parameters in young children by forced random noise.

The frequency dependence of total respiratory impedance during spontaneous breathing was measured repeatedly in 16 children (3--5 yr old) over a 3-mo period using forced random noise and spectral analysis. Total respiratory resistance, compliance, and inertance, which were calculated fromthe impedance data using regression analysis with a second-order model, had overall mean values +/- SD of 5.61 +/- 0.49 cmH2O.l-1.s, 403 +/- 1.04 ml.cmH2O-1, and 0.0120 +/- 0.0024 cmH2O.l-1.s2, respectively. Linear regression analysis showed that resistance and compliance correlated with either height or forced vital capacity with r values in the range 0.77--0.89. Analysis of measurement variability suggested that resistance measurements had, on the average, a coefficient of variation of 15%; corresponding values for compliance and inertance measurements were 25%.


Improved measurements of shear modulus and pleural membrane tension of the lung.

The continuum solution for the deformation of an elastic half space covered by a membrane is used to interpret measurements of the indentation of lung lobes under a column of fluid. The shear modulus mu of the underlying parenchyma is found to be approximately 0.7 times transpulmonary pressure, independent of species size. The tension in the pleural membrane T increases rapidly with increasing membrane area. For dog lungs, the value of T is 10(3) to 10(4) dyn/cm. For the larger species tested, pigs and horses, T is larger. The continuum solution shows that a concentrated force applied to the pleural surface is distributed over a distance T/mu as it is transmitted across the pleural membrane. The membrane is important in determining the displacement produced by forces that act within a region that is small compared to this distance, approximately 2 cm for dog lungs. By comparing the tension-area curve of the pleural membrane with the pressure-volume curve of the lobe, it is found that the pleural membrane contributes about 20% of the work done by the lung during deflation.


Distribution of regional volumes and ventilation in excised canine lobes.

A linear elasticity solution for the gravitational deformation of excised lungs was obtained. The accuracy of our solution was examined by comparing predicted and measured displacements of markers glued to the surface of canine lower lobes. The equations describing the strains in a lobe were used to predict the distribution of regional volumes and the slope of phase III (S3) of a single-breath oxygen (SBO2) test. The analysis predicted a negative S3. However, S3 was found to be positive in the five lobes tested, suggesting that factors other than gravity were responsible for the observed pattern of ventilation. In SBO2 tests repeated with increasing delays at end inflation, S3 progressively decreased, became negative, and was eventually abolished. Our equations predicted the most negative observed S3 well. We conclude that continuum mechanics can be used to describe the gravitational deformation of lungs and the resulting effect on ventilation distribution.


Influence of exercise and CO2 on breathing pattern of normal man.

Ventilatory patterns during rest, CO2 inhalation (2, 3, and 4%) and three levels of exercise were analyzed in supine men using a canopy system for noninvasive measurements. Changes in tidal volume (VT) and breathing frequency (f) with equal increases in minute ventilation (VE) differed significantly during exercise and CO2 inhalation. Increases in VE during exercise was accompanied by increases in VT and f. During CO2 inhalation, the change in frequency was less than during exercise. However, when analyzed in terms of inspiratory flow (VT/TI) and inspiratory duty cycle (TI/Ttot), the response to both stimuli was similar. With increases to twice control VE both TI/Ttot and VT/VI increased. Thereafter only VTTI increased with increasing VE. At rest, inspiratory time on a breath by breath basis increased minimally with VT, while changes in inspiratory flow accounted for the variability in VT. These two respiratory stimulants appear to increase ventilation through different mechanisms when analyzed in terms of VT and f. However, changes in inspiratory flow and duty cycle are similar in both.


Heat and acute dehydration effects on acceleration response in man.

Though heat and dehydration each impair acceleration tolerance, interactions among these stresses have not previously been studied. Seven men were dehydrated in heat by 0, 1, and 3% of body weight before a series of +Gz, gradual-onset centrifuge runs with the capsule first 38 degrees C, then 20 degrees C. Heat alone raised heart rate by 6.5 beats/min independent of other stresses. Dehydration and acceleration appeared to act synergistically in raising HR. Heat lowered relaxed G tolerance by 0.3 G; dehydration tended to lower G tolerance and increased the variability of response to heat. A high-tolerance subgroup (n = 4) could normally sustain +7 Gz for 60 s with anti-G suit and straining, but 3% dehydration reduced mean time to 35 s. Dehydration was associated with a decrease in the loss of plasma volume at 7 G. Heat-induced tolerance loss appears similar for both gradual- and rapid-onset centrifuge profiles. In contrast, dehydration effects are greater in rapid-onset runs, evidence that normal anti-G protective mechanisms can partly counteract the effect of fluid deficit. The results are relevant for crew members of high-performance aircraft, where unexpected diminution of their normally high G tolerance can have disastrous consequences.


Equation of motion of a cyclist.

Tractional resistance (RT, N) was determined by towing two cyclists on a racing bike in "fully dropped" posture in calm air on a flat track at constant speed (5--16.5 m/s). RT increased with the air velocity (v, m/s): RT = 3.2 + 0.19 V2. The constant 3.2 N is interpreted as the rolling resistance and the term increasing with v2 as the air resistance. For a given posture this is a function of the body surface (SA, m2), the air temperature (T, degree K), and barometric pressure (PB, Torr). The mechanical power output (W, W) can then be described as a function of the air (v) and ground (s) speed: W = 4.5.10(-2) Ps + 4.1.10(-2) SA (PB/T)v2 s, where P is the overall weight in kg. With a mechanical efficiency of 0.25, the energy expenditure rate (VO2, ml/s) is given by: VO2 = 8.6.10(-3) Ps + 7.8.10(-3) SA (PB/T)v2 s (1 ml O2 = 20.9 J). As the decrease of VO2max with altitude is known from the literature, this last equation allows the calculation of the optimal altitude for top aerobic performance. The prediction derived from this equation is consistent with the present 1-h world record.


Effects of endurance training on left ventricular dimensions in healthy men.

Echocardiography was employed to measure the serial effects of jogging on resting left ventricular dimensions and function. Twelve men were exercised (mean age 36.8 yr) and 10 served as controls (mean age 34.8 yr). Increases of 14 and 18% were observed for predicted aerobic capacity in the training group (TG) after 3 and 6 mo of training, respectively; the control group (CG) displayed a small detraining effect. Echocardiographic findings included a significant (P less than 0.05) reduction in resting heart rate and a moderate increase in stroke volume (SV) in the TG compared to the CG. The increased SV appeared to be due to increased end-diastolic dimensions (LVIDd, LVEDV), secondary to greater ventricular filling rather than a more vigorous ventricular contraction. Posterior wall thickness, septal thickness, and calculated left ventricular muscle mass were not significantly increased in the TG compared to CG after either 3 or 6 mo training. It was concluded that left ventricular structure and resting contractile status are not altered by 6 mo of jogging training in healthy, previously sedentary men.


Effect of heparin or fibrinogen depletion on lung fluid balance in sheep after emboli.

Investigators have proposed that fibrinogen, fibrin, or their degradation products are essential for the increased lung vascular permeability to fluid and protein that may occur after microemboli. To test this hypothesis, we used 20 anesthetized ventilated sheep in which we measured lung lymph flow, pulmonary artery and left atrial pressures, thermodilution cardiac output, and lymph/plasma protein concentrations. We injected glass bead microemboli (200 micrometers diam) sufficient to raise pulmonary vascular resistance to three times base-line values and cause increased lung lymph flow with a parallel increase in protein clearance, which is characteristic of increased lung vascular permeability. Neither large doses of heparin (3,000 U/kg) nor fibrinogen depletion with viper venom (ancrod, 2 U/kg), by themselves, affected steady-state pulmonary hemodynamics or lung fluid balance. These treatments prior to giving sufficient amounts of emboli to triple the pulmonary vascular resistance did not prevent the increased lung vascular permeability. We conclude that neither fibrin deposition nor degradation are essential to microembolic lung vascular injury in sheep.


Isobaric gas counterdiffusion in rabbit eye.

The superficial isobaric gas counterdiffusion phenomenon, which produces dermal lesions and lethal gas embolism, was investigated at sea level and 2 ATA for effects on the eye of the New Zealand White rabbit. The animals breathed an N2O-O2 mixture by mask and were surrounded by a He environment. There was no gas lesion formation in the conjunctiva or cornea and no gas bubble formation in the anterior compartment of the eye in any of the experimental animals, even at the maximal 8-h exposure. In contrast to the eye, the skin of these animals showed progressive gas-filled lesions after 3 h at 1 ATA. Reasons for the relative insensitivity of the structures of the eye to the counter-diffusion process are discussed.


Subcutaneous tissue gas space pressure during superficial isobaric counterdiffusion.

Changes in subcutaneous tissue pressure caused by N2O-He, 1-ATA isobaric counterdiffusion gas phase development were measured. Only the ears of New Zealand White rabbits were subjected to counterdiffusion. The rabbits breathed a mixture of 80% N2O-20% O2 while their ears alone were surrounded by He and the rest of their bodies continued to be surrounded by air. Subcutaneous pressure changes were transmitted to the transducer-recorded system via a fluid-filled subcutaneous needle. When the gas phase developed in subcutaneous tissue, pressure rose and a maximum pressure (Pmax) was reached. Pmax in the counterdiffused ear was 48 +/- 10 (SD) Torr, and mean time to reach Pmax was 75 +/- 10 (SD) min. The findings are discussed in relation to the pathological processes of isobaric inert gas counterdiffusion.


Effect of inhalate thermal conductivity and high O2 in producing hypothermia.

The effect of an increase in inhalate thermal conductivity and the fraction of inspiratory O2 (FIO2) on the rate of cooling and rewarming using a surface-inhalate heat exchange method was evaluated. Male New Zealand White rabbits were divided into three groups: those ventilated with air, those with 20% O2 + 80% He, and those with 100% O2. All animals were cooled to an esophageal temperature of 22.5 degrees C (or for 180 min maximum). Following a 15-min exposure to room air, the animals were connected to the humidifying and warming system. He-O2 had the highest thermal conductivity and the animals ventilated with it had the fastest cooling rate. One hundred percent O2 and room air had similar thermal conductivities, but the animals ventilated with 100% O2 had significantly lower cooling rates. These data indicate that, while maintaining a constant surface heart exchange, the rate of heat exchange across the lung can be modified by altering the thermal conductivity of the inhalate gas mixture. Total heat exchange can also be modified by hyperoxemia-induced hemodynamic changes.


Initiation of each avian inspiration by a CO2 threshold mechanism.

The avian respiratory oscillator has been investigated in a unidirectionally ventilated chicken by changing the dynamic pattern of inflow CO2 concentration (FCO2). Stimulation with periodic FCO2 results in a one-to-one synchronization of the respiratory movements that we have called pacing (Respir. Physiol. 22: 167--177, 1974). A two-parameter CO2 threshold model is proposed to explain this behavior. The model states that when FCO2 reaches a threshold level (L), it initiates the beginning of inspiration a constant time interval (LB) later. According to this model, when a triangular FCO2 concentration is used to synchronize the breathing pattern, the time from the minimum of the wave form to the beginning of inspiration (C-B interval) is dependent on the mean value and the rate of rise of FCO2 as determined by period and amplitude of the triangle. Particularly interesting is the prediction that the direction of the relationship (increasing or decreasing) between FCO2 amplitude and the C-B interval is dependent on whether the mean value of FCO2 is above or below the threshold level. Experimental data obtained during amplitude changes support the above prediction.


A closed lung system study of inert gas absorption.

The demonstration that the rate of rise of the alveolar fraction of nitrous oxide is enhanced when the inspired N2O concentration is high is termed the "concentration effect." A similar effect on a second gas has been termed the "second gas effect". These effects have been observed in open systems and attributed to differential changes between inspired and expired ventilation. The purpose of this investigation is to study these effects in a closed system. A breath-holding maneuver was utilized with a high and a low N2O concentration in argon and oxygen. The results indicate that breath holding with a high N2O concentration "concentrates" both the alveolar fraction of N2O and argon. These results are attributable to alveolar volume shrinkage as a consequence of the large absorption of N2O by the pulmonary blood. A mathematical model verifies this interpretation and suggests that volume shrinkage can be important in breath-holding maneuvers designed for noninvasive measurement of cardiac output and lung tissue volume.


Effect of methacholine chloride on rheology and transport of canine tracheal mucus.

The effect of methacholine chloride (M) on tracheal mucus was investigated in three conscious tracheostomized dogs. Aerosols of M in concentrations of 2--32 mg/ml were delivered intratracheally for 1 min. Mucus was sampled with a cytology brush at 2 min postchallenge and at irregular intervals thereafter. The mechanical properties of each sample were determined in the magnetic microrheometer, and correlated with mucociliary transportability as assayed by the frog palate technique. With high doses of M, there was an increase in volume of secretion collected per unit time. The elastic modulus (G') at 2 min postchallenge went up (to 1.5 x 2.3 x control for 16 and 32 mg/ml, respectively) then fell below control before returning to base line after 30 or 45 min. With low doses of M (2--8 mg/ml) the secretion rate was also above control, but only a decrease in G' (to 0.54 x control) was observed. The decrease in G' at low doses did not significantly alter the frog palate transport rate; however, the increase at higher doses did impede mucociliary transport.


Diffusing capacity at different lung volumes during breath holding and rebreathing.

Single-breath diffusing capacity of the lung for carbon monoxide (DLCO) increases as lung volume increases above functional residual capacity (FRC). However, the physiological mechanism responsible for this increase remains controversial. This volume dependence of diffusing capacity could reflect changing regional distribution of inspired air as lung volume increases rather than a change in capillary blood volume or surface area for gas exchange. We measured DLCO during breath holding and during rebreathing with a technique employed to mix respired gases throughout the lung thereby minimizing regional distribution differences. Measurements were made 1,500 ml above FRC and near total lung capacity (TLC). Breath holding DLCO was 18% higher near TLC than at 1,500 ml above FRC (P less than 0.05). Rebreathing DLCO was 16% higher near TCL than at 1,500 ml above FRC (P less than 0.01). Equality of results by the two techniques indicates that changes in DLCO with lung volume are not a consequence of the changing distribution of inspired air. Our results are compatible with the hypothesis that effective surface area of the lung increases as lung volume expands.


Thoracoabdominal mechanics during relaxed and forced vital capacity.

Thoracoabdominal configuration, intrathoracic (esophageal), intra-abdominal (gastric), and transdiaphragmatic pressures were studied in six normal upright subjects during relaxed (RVC) and forced vital capacity (FVC). Chest wall configuration showed substantial departure from its relaxation characteristics during FVC. Paradoxical (outward) movement was recorded for a low lateral diameter of the rib cage (on the costal margin) at high volume during RVC and during most of FVC, while the other rib cage dimensions were decreasing. Transdiaphragmatic pressure was positive during most of the FVC, particularly toward RV, reflecting active contraction of the diaphragm. We conclude that diaphragmatic activity modulates forced expiration and that the chest wall may influence the FVC maneuver.


Variability of airway responses to inhaled histamine in normal subjects.

Dose-response curves to inhaled histamine were studied in 12 normal subjects. Pulmonary resistance (RL) and dynamic compliance (Cdyn) were measured during tidal breathing, and maximum expiratory flow rates, at an absolute lung volume corresponding to 40% of control vital capacity, were obtained during forced expiration from tidal end inspiration (Vmax40p) and from total lung capacity (Vmax40c). Threshold was defined as the histamine dose at which a departure from the range of normal measurements was observed. RL and Vmax40p indicated lowest threshold values, which varied by a factor of 32 and 38, respectively. There was no correlation between reactivity, which reflects the slope of the dose-response curve beyond the threshold dose, and threshold doses, nor between the initial RL (normalized for lung volume) and either threshold or reactivity. In eight subjects, restudied on two occasions after 10 mg propranolol or after saline, injected in a double-blind manner, there was no change in the dose-response curves. These results indicate that different indices of bronchoconstriction may yield different dose-response curves and hence different sensitivities. In addition, a wide variation of airway responses to inhaled histamine exists in the normal population and beta-blockade does not influence this variability.


Tolerance of estrogen-treated rats to acute cold exposure.

Female rats treated chronically with ethynylestradiol (36 micrograms/kg per day) alone, and in combination with the progestational agent, norethynodrel (253 micrograms/kg per day), cooled significantly faster than controls when lightly restrained and exposed to air at 5 degrees C. Rate of cooling of rats given only norethynodrel was similar to that of the control group. In other studies, rate of oxygen consumption was determined for all groups during acute exposure to cold (14 degrees C). All estrogen-treated groups achieved the same maximal rate of oxygen consumption as control and norethynodrel-treated groups during cold exposure, but cooled significantly faster. Two groups of female rats were treated chronically with ethynylestradiol at two separate doses (36 and 61 micrograms/kg per day). An untreated group served as controls. Rate of oxygen consumption of all animals were measured during restraint and exposure to cold (18 degrees C). The estrogen-treated groups again achieved the same maximal rate of oxygen consumption as the control group, but also cooled significantly faster despite the fact that the cold stress was less severe than in the previous experiment. That estrogen-treated rats cooled faster than controls in both studies despite achieving a maximal rate of heat production which did not differ from controls suggests that reduced cold tolerance of estrogen-treated rats may be related to increased heat loss.


Gas-to-blood PCO2 differences during severe hypercapnia.

Five anesthetized dogs were made severely hypercapnic by stepwise addition of CO2 to their inspired air. Blood PCO2 levels greater than 400 Torr were reached. During hypercapnia, the steady-state end-tidal PCO2 (PaCO2) was always higher than the simultaneous measured arterial PCO2 (PaCO2). The mean ratio PaCO2/PACO2 was 0.861 +/- 0.01. These results are consistent with the predictions of the Charged Membrane Hypothesis, that gas-to-blood PCO2 differences should be directly proportional to the blood H+ activity. The results cannot be explained by delayed equilibration of CO2 between plasma and red blood cells. The latter hypothesis predicts that, under the conditions of these experiments, the PCO2 of arterial blood should be higher than the PCO2 of end-tibal gas. The blood HCO3- during hypercapnia did not increase as much as would be predicted if the blood were exposed to CO2 in vitro. This may reflect movement of blood HCO3- generated by the buffering of carbonic acid into intracellular compartments during hypercapnia.


Protein metabolism in lung: use of isolated perfused lung to study protein degradation.

This study investigates the use of the isolated perfused lung to study protein degradation. Proteins were labeled in vivo for 10 min or for 5 h using L-[U-14C]phenylalanine. When prelabeled lungs were perfused in vitro virtually all of the acid-soluble and acid-insoluble radioactivity in the tissue and perfusate remained as phenylalanine. Protein degradation was measured as the accumulation of free [14C]phenylalanine in ther perfusate; during the time this accumulated the amount of intracellular free phenylalanine and the free phenylalanine space remained constant. Proteins labeled during 10 min had a constant rate of degradation between 45 and 90 min of perfusion (about 11%.h-1); those labeled during 5 h had a constant rate of degradation for 90 (about 3%.h-1). The percent dry lung weight did not change during the perfusion. We conclude that measurable rates of proteolysis of "rapid" and "slowly" turning over proteins can be obtained while the lung is virtually free of edema. This system should allow studies on the modulation of proteolysis in intact lung under defined conditions.


Degradation of endogenous protein by rabbit pulmonary macrophages.

Pulmonary macrophages were preincubated for 1 or 20 h with L-[U-14C]phenylalanine and the degradation of labeled proteins studied by reincubating these cells in the presence of 4 mM  L-phenylalanine and measuring rates of [14C]phenylalanine released from the cells into the medium. We found that proteins prelabeled in 1 or 20 h were degraded 8.0 and 3.0%.h-1, respectively. Decreases in cell viability reduced the rate of protein degradation. Lack of exogenous glucose slowed the rate of degradation of proteins labeled in 1 h, but not of those labeled in 20 h. Varying amino acids in the medium from normal to 5 times normal rabbit plasma levels had no effect on the degradation of either group of proteins. Rates of degradation of both fast and slowly turning over proteins were inhibited during phagocytosis of polystyrene latex particles by about 62 and 33%, respectively. The time course of the changes in protein degradation suggests they are related to intracellular events in the phagocytic process, rather than particle attachment or uptake.


Pattern and mechanism of airway response to hypocapnia in normal subjects.

We examined the bronchoconstriction produced by airway hypocapnia in normal subjects. Maximal expiratory flow at 25% vital capacity on partial expiratory flow-volume (PEFV) curves fell during hypocapnia both on air and on an 80% helium- 20% oxygen mixture. Density dependence also fell, suggesting predominantly small airway constriction. The changes seen on PEFV curves were not found on maximal expiratory flow-volume curves, indicating the inhalation to total lung capacity substantially reversed the constriction. Pretreatment with a beta-sympathomimetic agent blocked the response, whereas atropine pretreatment did not, suggesting that hypocapnia affects airway smooth muscle directly, not via cholinergic efferents.


Intestinal transport of hexoses in the rat following chronic heat exposure.

The effect of 3 wk heat exposure (Ta 34 degrees C) on intestinal weight and intestinal absorption of D-glucose and D-galactose in vitro was examined in the rat. Intestinal dry weight was reduced with heat exposure compared to both ad libitum and pair-fed animals at Ta 22 degrees C. Intestinal tissue water was elevated after pair feeding but not heat exposure; extracellular (inulin) space was similar in the three groups. Mucosal uptake of glucose per gram wet weight in an everted sac preparation was unchanged compared to pair-fed animals, but serosal transfer was increased. Intestinal metabolism of glucose was decreased with heat exposure. Galactose accumulation with 30 min incubation was increased in intestinal rings from both heat-exposed and pair-fed animals. This increase is likely to be related to the reduction in ring size present in the groups with reduced food intake. Vmax and apparent Km for galactose transport were unchanged. Our results indicate that despite a reduction in intestinal weight following heat exposure, the ability of the intestine to transport hexoses per gram remains relatively stable. Alterations of hexose transport appear to be related to altered glucose metabolism and not altered transport capacity. Differences in intestinal weight and glucose utilization between pair-fed and heat-exposed animals suggest that the intestinal response to chronic heat exposure is not solely a function at the amount of food consumed. However, the alteration of more than one variable in pair feeding makes interpretation complex.


Phrenic activity during severe hypercapnia in vagotomized rabbits.

The central control mechanism of respiratory frequency under varied alveolar carbon dioxide pressure (PACO2 20--200 Torr) was investigated in anesthetized, vagotomized, immobilized, and artificially ventilated rabbits. Central inspiratory activity indicated by phrenic motor discharge was tolerant of the extensive hypercapnia. Under light anesthesia the respiratory frequency (f) decreased in a hyperbolic fashion with increasing PACO2. Under deeper anesthesia or after mesencephalic decerebration the hyperbolic f response to PACO2 was abolished or changed to a hill-type f response (initial increase and subsequent decrease in f) and, on the average, the changes in frequency were much less. We conclude that in the absence of vagal control the respiratory frequency is primarily determined by 1) the periodicity of the bulbopontine inspiratory activity, which is little dependent on PACO2, and 2) a suprapontine acceleratory mechanism, which is depressed by increased PACO2 and highly sensitive to anesthetics. The mechanism of changes in the type of f response to CO2 is discussed.


Absence of effects of hypoxia on small airway function in humans.

We measured the effects of sustained isocapnic hypoxia (PAO2 = 40--50 Torr; PACO2 = 38--42 Torr) on tests sensitive to small airway function in healthy human subjects. Maximum expiratory flow-volume curves on air, nitrogen-hypoxic, helium-normoxic, and helium-hypoxic mixtures as well as closing volumes while subjects breathed air and a hypoxic mixture were obtained. We then measured total lung capacity (TLC), both plethysmographically and by inert gas dilution, and used the nonplethysmographic method to measure the effects of hypoxia on TLC. In none of these tests were there any statistically significant changes when values obtained during hypoxia were compared with those during normoxia. It is suggested that previous reports that indicated that TLC was increased by hypoxia might have arisen from a plethysmographic artifact.


Cardiac effects of increased lung volume and decreased pleural pressure in man.

The cardiac effects of increased lung volume and/or decreased intrathoracic pressure were assessed by radionuclide angiography in normal male subjects. Increased lung volume alone produced no change in left ventricular (LV) or right ventricular (RV) end-diastolic size. Decreasing intrathoracic pressure to -30 Torr with a Mueller maneuver led to increases in LV end-diastolic and end-systolic volumes, and to increases in RV diastolic area. LV ejection fraction did not change significantly but RV ejection fraction decreased with the Mueller maneuver. Increases in transmural central venous pressure were also noted with the Mueller maneuver. The effects of combining increased lung volume with the Mueller maneuver were similar to those with the Mueller maneuver alone. These effects are consistent with the hypothesis that producing large negative pleural pressures acts to impede left ventricular outflow (i.e., afterloading) and raises the possibility of similar changes during acute attacks of bronchospasm.


Mechanical efficiency of fast- and slow-twitch muscle fibers in man during cycling.

The influence of different percentages of slow-twitch (ST) and fast-twitch (FT) fibers in vastus lateralis on delta efficiency expressed by delta work (x)/delta energy liberation (y) in y = a + bx was studied in six subjects during cycling on an ergometer at 60 or 100 rpm at work loads below 80% of VO2max. Three subjects had an average of 78% ST fibers (ST group) and the other subjects had an average of 76% FT fibers (FT group). There was no difference between the two groups in delta efficiency at 60 rpm, but at 100 rpm the efficiency of the ST group was significantly lower than that of the FT group (19.6 vs. 28.8%, P less than 0.01). In the ST group respiratory exchange ratio (R) was higher at 100 rpm than at 60 rpm, but the FT group had similar R values at both pedal revolution rates. The most important finding was the reduced efficiency when pedaling frequency was increased from 60 to 100 rpm in the ST group (23.3 to 19.6%). Predominant use of ST fibers at rapid pedal rates may require a substantial increase in energy expenditure.


Frequency dependence of respiratory resistance in healthy children.

We measured in 130 (61 girls) children aged 3--14 yr respiratory resistance (Rrs), with the oscillation technique, between 4 and 9 Hz. Rrs, at both 4 and 9 Hz, decreased as a function of height (r = 0.74, P less than 0.001). No statistical difference was found between boys and girls. Frequency dependence of resistance (Rrs 4 Hz-Rrs 9 Hz) was found in children at all ages, and decreased with increasing height (r = 0.50, P less than 0.001). We suggest that frequency dependence of resistance in children can be explained on the basis of an increased peripheral resistance, which produces an asynchronous distribution of tidal volume between dead space and lung parenchyma. During growth peripheral resistance decreases and Rrs bcome less frequency dependent to reach at about 15--16 yr independency of frequence.


Effect of somatostatin on plasma glucagon and insulin, and glucose turnover in exercising sheep.

To examine the roles of glucagon and insulin in exercise, four sheep were run on a treadmill with and without simultaneous infusion of somatostatin (SRIF), a peptide that suppresses glucagon and insulin secretion. SRIF infusion suppressed the exercise-induced rise in plasma glucagon during both moderate (5--5.5 km/h) and strenuous exercise (7.0 km/h). In addition, SRIF prevented the rise insulin concentrations during moderate exercise. During strenuous exercise, insulin concentrations were depressed in both groups. The infusion of SRIF was associated with a reduction in exercise-induced glucose production, as determined by infusion of [6-3H]glucose, during the first 15 min of both moderate and strenuous exercise compared to controls. Beyond 15 min glucose production was not significantly altered by SRIF infusions. These data are consistent with glucagon having an immediate, but only transient, stimulatory effect on the exercise-induced hepatic glucose production.


Effect of rate of change in skin temperature on local sweating rate.

To evaluate the relative contributions of positive and negative variations of mean skin temperature (+/- dTsk/dt) on thermoregulatory responses, male resting nude subjects were exposed to rapid or slow alterations in air and wall temperatures (28--45 degrees C; Pa = 20.0 mbar). Rates of heating-cooling cycles were equal to dTa/dt = +/- 3.40, 1.13, 0.57, 0.38, or 0.19 degrees C/min. Continuous measurements were made of rectal, oral, ear, and mean skin temperatures and of arm sweating (dew-point hygrometer method). During all exposures the local skin temperature was kept constant (Tsl = 39 degrees C). The results showed that peripheral inputs are a major factor in thermoregulatory processes. Cutaneous receptors produce a positive and a negative rate component within the central thermal integrator. A higher rate threshold was observed for the positive rate component than for the negative one.


Apnea, tachypnea, and hypotension elicited by cardiac vagal afferents.

The reflex effects of right and left ventricular distension, mediated by vagal afferents, were studied in mongrel dogs anesthetized with halothane or pentobarbital sodium on heart-lung bypass. Diaphragm electromyogram (D-EMG), systemic blood pressure, and left ventricular cardiogram were all measured during ventricular distension. After bilateral section of the stellate ganglia, distension of the left ventricle produced an apnea, or slowing of respiration and systemic hypotension, without a change in heart rate. A reflex decrease in the amplitude of the D-EMG occurred if the initial breathing rate was high; a decrease in frequency of the D-EMG bursts occurred if the initial rate was low. The left ventricular vagal afferents altering respiration had conduction velocities between 22 and 70 m/s, whereas those causing hypotension had conduction velocities less than 22 m/s. Distension of the right ventricle resulted in a significant tachypnea and systemic hypotension without a change in heart rate. The conduction velocities of the right ventricular vagal afferents causing both tachypnea and hypotension were less than 9 m/s. These reflex changes in respiration and blood pressure elicited by both right and left ventricular distension were eliminated with vagotomy.


Measurements of the dead space volume.

The "anatomical" dead space is commonly measured by sampling an inert gas (N2) and volume in the exhalation following a large breath of oxygen (VD(F)). It may also be measured from an inert gas washout (VD(O)) that describes both volume and the delivery of VD(O) throughout the expiration. VD(O) is known to increase with age and is enlarged in some obstructive syndromes. VD(O) was appreciably larger than VD(F) in our normal subjects. Both measures increased with lung volume, the increase being entirely due to an increase in the volume of phase I. Physiological dead space (VD(p)) however, did not change significantly with lung volume, showing "alveolar" dead space to diminish as a result. An increase in VD(O) occurred with increasing respiratory frequency that was explained by the increase in volume of phase I. Although an increase in VD(F) occurred with frequency, this was significantly less than that seen by VD(O), i.e., VD(F) did not see the progressive increase in phase I volume with frequency. No lung volume or frequency changes, parasympatholytic or sympathomimetic drugs, or altered patterns of breathing simulated the late delivery of dead space seen in age and some obstructive syndromes.


In situ perfusion of rat lungs: stability and effects of oxygen tension.

A new method for perfusion of rat lungs in situ was developed for metabolic studies. The pulmonary circulation was cannulated without contacting the lungs, which remained in the thoracic cage. Perfusion was continued for up to 4 h with Krebs-Henseleit bicarbonate buffer, equilibrated with 95% O2- 5% CO2 and containing 4.5% bovine serum albumin, 5.6 mM glucose, and levels of amino acids normally found in rat plasma. At an arterial pressure of 20 cmH2O flow remained constant (10.9 ml/min.100 g body wt) and appeared evenly distributed among the lobes. Tidal volume was 1 ml/100 g body wt (72/min); positive end-expiratory pressure was 2 cmH2O. The preparation remained stable and metabolically active for 4 h, as evidenced by a minimal decline in dry-to-wet weight ratio, constant levels of ATP and glycogen, a high ratio of glucose uptake to lactate production, and a linear rate of incorporation of [14C]phenylalanine into protein. The lungs were unaffected when perfusate oxygen was reduced to a more physiological level (20% O2-75% N2-5% CO2). In the presence of 95% N2-5% CO2 dry-to-wet weight ratio, ATP, glycogen, and amino acid incorporation decreased, while lactate production doubled.


Mechanisms of airway smooth muscle response to isoproterenol and theophylline.

Airway smooth muscle preparations from various sites and species exhibit a range of sensitivities to the same beta-adrenergic agonist. This variability has been attributed to beta-receptor function but the exact mechanism determining the response has not been identified. After first inducing contraction with acetylcholine, we measured isoproterenol and theophylline relaxation responses in five separate airway smooth muscle preparations in vitro. The order of sensitivity was identical for both drugs: guinea pig trachea greater than dog lung strip greater than dog bronchiole greater than rat trachea greater than dog trachea. Because of evidence that both drugs act by increasing adenosine 3',5'-cyclic monophosphate (cAMP) concentrations, we utilized a kinetic model of cAMP metabolism to investigate the possibility that the identical order of sensitivity to both drugs could be explained by a common mechanism. Relaxation responses to both drugs are in accord with known kinetic data. Small differences in the velocity constants of enzymes affecting cAMP metabolism or differences in the relaxation response to the same concentrations of cAMP can fully explain the variable muscle responses to both drugs.


Oxygen affinity of blood in altitude Sherpas.

Oxygen equilibrium curves on blood within 6 h from sampling have been estimated from polarographic measurements of oxyhemoglobin concentration, in 13 male 14- to 50-yr old Sherpas residing at 3,850 m above sea level (Kumjung, Nepal). In samples with red blood cell counts = 4.7 +/- 0.8 (SD) x 10(6)/mm3, total hemoglobin concentration [Hb] = 17.0 +/- 1.9 g/dl, and hematocrit = 53.3 +/- 5.0, the mean oxygen half-saturation of hemoglobin (P50) (pH = 7.4 and PCO2 = 40 Torr) was 27.3 +/- 1.8 Torr. The P50 of altitude Sherpas was not significantly different from that of acclimatized lowlanders (28.2 +/- 1.3; n = 7), sea-level Caucasian residents (26.5 +/- 1.0; n = 17), and Sherpas at sea level (27.1; n = 3). The 2,3-diphosphoglyceric acid-to-hemoglobin concentration ratio ([2,3-DPG]/[Hb]) in altitude Sherpas was 1.22 +/- 0.03, the same as that of acclimatized Caucasians (1.22 +/- 0.10). The Bohr effect measured for the blood of one altitude Sherpas by the ratio deltalog P50/deltapH was -0.32 and -0.45 at PCO2 levels of 40 and 20 Torr, respectively. These values are not significantly different from those found in Caucasians at sea level where deltalog P50/deltalpH was -0.35 and -0.42, respectively. It is concluded that the P50 in native highlanders is not significantly different from that observed in sea-level dwellers. [2,3-DPG]/[Hb] at altitude, both in natives and in newcomers, is 20% higher than in sea-level residents.


Calorigenic effect of insulin in hypothermic dogs.

In dogs acutely immersed in cold water (8--13 degrees C), oxygen uptake increased approximately sevenfold and colonic temperature rapidly began to decrease. Fifteen minutes after the start of immersion a high level of hyperglycemia was found but no increase in immunoreactive plasma insulin level was observed. Under these conditions exogenous insulin (0.3 U.kg-1) induced a further increase in oxygen uptake and in shivering intensity whereas a decrease in the fall of colonic temperature was observed. It can be concluded that insulin may have a calorigenic effect and improve the resistance to cold of dogs exposed to an acute cold stress.


Impedance of intrathoracic airway models during low-frequency periodic flow.

The total pulmonary and lower airway impedances of the normal adult lung were simulated from 0.5 to 10 Hz using a distributed parameter model of the complete tracheobronchial tree. The model includes branching asymmetry; distributed representation of gas compliance, inertance, viscous effects, and inertial distortion of velocity profiles; and nonrigid airway walls. The model predicts closely similar resistance and frequency dependence of resistance but substantially greater reactances than observed by Finucane et al. (J. Appl. Physiol. 38: 517--530, 1975). Increases in resistance with frequency could be explained by changes in the distribution of flow among parallel inhomogeneities (47%), inertial distortion of velocity profiles (35%), changes in the serial distribution of flow due to gas compliance (11%), and airway wall compliance (7%). The disparity between measured and simulated reactance is attirbutable to artifact in the previously reported reactance measurement.


Cardiorespiratory responses following isoproterenol injection in rabbits.

Receptor sites for the ventilatory response to isoproterenol were investigated in anesthetized rabbits with bolus injections in the common carotid artery (ia) and in the vena cava (iv). The delay from injection to the increase in ventilation (TVE) was significantly shorter following ia (1.5 s) compared to iv injections (about 5 s). The delay to the increase in heart rate (THR) was significantly shorter after iv (about 4.5 s) than after ia injections (12.5 s). When isoproterenol and NaCN injections were compared, there was no difference in TVE. Following carotid body resection, the VE response to isoproterenol was greatly reduced after iv and ia injections; however, THR was unaffected. In intact animals breathing 100% O2 the VE response to isoproterenol was significantly reduced with no change in TVE or in the heart rate response. We conclude that the ventilatory increase following the injection of isoproterenol is due primarily to direct stimulation of the carotid bodies.


Rheological properties of excised rabbit lung stiffened by repeated hyperinflation.

Two rheological properties, stress adpatation (S) and hysteresis loop area (H), were studied in normal fresh rabbit lungs and in lungs stiffened by 3 hr repeated inflation at zero end-expiratory pressure. S was measured on the deflation limb at various volume levels ranging from 100 to 25% total lung capacity (TLC). H was obtained in another group of lungs before and after stiffening, for tidal volumes ranging from 5 to 30% TLC, at end-expiratory levels from 25 to 70% TLC. In stiff lung, S after deflation from TLC was biphasic (initial pressure rise, then a fall) whenever the starting pressure exceeded approximately 10 cmH2O. At low lung volumes (25% TLC) stress rose monotonically toward 10 cmH2O. Only monontonic adaptation has previously been reported for normal lung. Tidal H in stiff lungs was increased at all volume levels, occupying roughly 20% of a bounding pressure-volume rectangle, resembling that of normal lungs near TLC but twice that of normal loops at lower volumes. The results suggest that above an equilibrium or transition pressure around 10 cmH2O the alveolar lining in stiff lung may have film properties more resembling those of a viscous liquid, becoming solidlike below this pressure. Similar viscous liquid properties appear to exist on the inflation limb of normal lungs, and near TLC on their deflation limb.


Capillary recruitment during airway hypoxia: role of pulmonary artery pressure.

Hypoxia has been shown to cause an increased number of pulmonary capillaries to be perfused. Changes in cardiac output and left atrial pressure have been previously ruled out as causes of this capillary recruitment. Increased pulmonary vein pressure and increased pulmonary artery pressure remain as two potential mechanisms. To differentiate between these two possible causes, we measured pulmonary artery and vein pressures with directly placed catheters and capillary recruitment with in vivo microscopy. During isocapnic hypoxia pulmonary artery pressure doubled, observed capillary recruitment increased fivefold, and pulmonary vein pressure remained constant. When the vasodilator prostaglandin E1 was infused during hypoxia, pulmonary artery pressure and capillary recruitment fell to control values and pulmonary vein pressure remained constant. Since capillary recruitment correlated with pulmonary artery pressure in each dog, but not with pulmonary vein pressure, we conclude that arterial, not venous, constriction is the probable cause of this recruitment.