Variations in exercise ventilation in hypoxia will affect oxygen uptake.

Reports of VO2 response differences between normoxia and hypoxia during incremental exercise do not agree. In this study VO2 and VE were obtained from 15-s averages at identical work rates during continuous incremental cycle exercise in 8 subjects under ambient pressure (633 mmHg ≈1,600 m) and during duplicate tests in acute hypobaric hypoxia (455 mmHg ≈4,350 m), ranging from 49 to 100% of VO2 peak in hypoxia and 42-87% of VO2 peak in normoxia. The average VO2 was 96 mL/min (619 mL) lower at 455 mmHg (n.s. P = 0.15) during ramp exercises. Individual response points were better described by polynomial than linear equations (mL/min/W). The VE was greater in hypoxia, with marked individual variation in the differences which correlated significantly and directly with the VO2 difference between 455 mmHg and 633 mmHg (P = 0.002), likely related to work of breathing (Wb). The greater VE at 455 mmHg resulted from a greater breathing frequency. When a subject's hypoxic ventilatory response is high, the extra work of breathing reduces mechanical efficiency (E). Mean ∆E calculated from individual linear slopes was 27.7 and 30.3% at 633 and 455 mmHg, respectively (n.s.). Gross efficiency (GE) calculated from mean VO2 and work rate and correcting for Wb from a VE-VO2 relationship reported previously, gave corresponding values of 20.6 and 21.8 (P = 0.05). Individual variation in VE among individuals overshadows average trends, as also apparent from other reports comparing hypoxia and normoxia during progressive exercise and must be considered in such studies.

VESTPD as a measure of ventilatory acclimatization to hypobaric hypoxia.

This study compared the ventilation response to an incremental ergometer exercise at two altitudes: 633 mmHg (resident altitude = 1,600 m) and following acute decompression to 455 mmHg (≈4,350 m altitude) in eight male cyclists and runners. At 455 mmHg, the VESTPD at RER <1.0 was significantly lower and the VEBTPS was higher because of higher breathing frequency; at VO2max, both VESTPD and VEBTPS were not significantly different. As percent of VO2max, the VEBTPS was nearly identical and VESTPD was 30% lower throughout the exercise at 455 mmHg. The lower VESTPD at lower pressure differs from two classical studies of acclimatized subjects (Silver Hut and OEII), where VESTPD at submaximal workloads was maintained or increased above that at sea level. The lower VESTPD at 455 mmHg in unacclimatized subjects at submaximal workloads results from acute respiratory alkalosis due to the initial fall in HbO2 (≈0.17 pHa units), reduction in PACO2 (≈5 mmHg) and higher PAO2 throughout the exercise, which are partially pre-established during acclimatization. Regression equations from these studies predict VESTPD from VO2 and PB in unacclimatized and acclimatized subjects. The attainment of ventilatory acclimatization to altitude can be estimated from the measured vs. predicted difference in VESTPD at low workloads after arrival at altitude.

Plasma volume after heat acclimation: Variations due to season, fitness and methods of measurement.

PURPOSE: The reported magnitude of plasma volume increase (Δ%PV) following heat acclimation (HA) varies widely. Variations may result from differences in measurement techniques, season and subjects' fitness. This report compares direct and indirect measurements of Δ%PV after 10 days of HA from studies in winter (WIN, n = 8) and summer (SUM, n = 10) in men, age 21-43 yr, at two fitness levels (VO(2)max: 35 and 51 ml/min/kg). Direct measurements were made before and after HA (cycling at 30% of VO(2)max at 50 °C, for 100 min/day) by carbon monoxide (CO) rebreathing and compared with indirect estimates from changes in hematocrit, hemoglobin and plasma protein concentration. RESULTS: Overall, Δ%PV by CO was small (2.9%) and greater in SUM than WIN (5.0 vs. 0.3%). Red cell, blood and plasma volumes/kg lean body mass increased in SUM and decreased in WIN, the difference being significant, and Δ%PV by CO was similar for high and low VO(2)max. CONCLUSION: Overall, indirect estimates of Δ%PV by hemoglobin and hematocrit were similar to CO, but tended to differentiate by fitness and not season. The difference in THb increase in SUM and decrease in WIN was significant. This probably accounts for the differences from the seasonal and fitness results by the direct CO method.

Does heat acclimation improve exercise capacity at altitude? A cross-tolerance model.

New approaches to inducing altitude acclimation in a relatively short timeframe are needed, as it is not practical for many soldiers and athletes to gain access to specialized training facilities. Acclimation to one environmental stressor could enhance adaptation to various other stressors in animals and humans. This phenomenon has been described as cross-tolerance and involves the activation of common protective pathways. The purpose of this review is to discuss possible mechanisms involved in the cross-tolerance between heat and hypoxia. Future data could potentially support the use of a cross-tolerance model as a means for military personnel to prepare for deployment to high-altitude environments, as well as for athletes competing at high altitude.

Ventilation is greater in women than men, but the increase during acute altitude hypoxia is the same.

We wished to determine whether the previously reported lower arterial or alveolar P(CO2) in women than men, and in luteal (LUT) compared with follicular (FOL) menstrual cycle phase would persist during normal oral contraceptive use and during early altitude exposure. Ventilation and blood gases were measured at baseline (636 mmHg approximately 5400 ft, 1650 m) and during simulated altitude at 426 mmHg ( approximately 16000 ft, 4880 m), after 1 h (A1) and during the 12th h (A12), in 18 men (once) and in 19 women twice, during LUT and FOL and in 20 women twice while on placebo (PLA) or highest progestin dose (PIL) oral contraceptives. At baseline, Pa(CO2) was significantly higher in men than all women by 3.3 mmHg. When progesterone-progestin (PRO) was elevated in women, Pa(CO2) was significantly lower than in FOL and PLA, but the latter were still significantly lower than men. At altitude the P(CO2) differences between men and women and PRO levels persisted, with PA(CO2) falling by 3.6 and 7.3 mmHg at A1 and A12 in all, indicating an equivalent increase in alveolar ventilation. The mean arterial-end tidal P(CO2) difference was never >2 mmHg in the groups, indicating no VA/Q mismatch related to gender, PRO levels or altitude. All women had higher breathing frequency than men, resulting in greater deadspace ventilation. At altitude, the mean Pa(O2) was approximately 44 mmHg (Sa(O2) approximately 79%) for all, indicating equivalent oxygenation, but alveolar-arterial P(O2) differences were greater in women than men and higher when PRO was elevated. These results show that, relative to men, women have a compensated respiratory alkalosis, accentuated with elevated PRO. However, the ventilation response to acute altitude is the same in women and men.

Exercise exacerbates acute mountain sickness at simulated high altitude.

We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitude in a decompression chamber [barometric pressure = 429 Torr, approximately 4,800 m (J. B. West, J. Appl. Physiol. 81: 1850-1854, 1996)], seven men exercised (Ex) at 50% of their altitude-specific maximal workload four times for 30 min in the first 6 h of a 10-h exposure. On another day they completed the same protocol but were sedentary (Sed). Measurements included an AMS symptom score, resting minute ventilation (VE), pulmonary function, arterial oxygen saturation (Sa(O(2))), fluid input, and urine volume. Symptoms of AMS were worse in Ex than Sed, with peak AMS scores of 4.4 +/- 1.0 and 1.3 +/- 0.4 in Ex and Sed, respectively (P < 0.01); but resting VE and Sa(O(2)) were not different between trials. However, Sa(O(2)) during the exercise bouts in Ex was at 76.3 +/- 1.7%, lower than during either Sed or at rest in Ex (81.4 +/- 1.8 and 82.2 +/- 2.6%, respectively, P < 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3-6 h (P = 0.06). The mechanism(s) responsible for the rise in severity and incidence of AMS in Ex may be sought in the observed exercise-induced exaggeration of arterial hypoxemia, in the minor fluid shift, or in a combination of these factors.

Effects of gas density on experimentally obstructed ventilation during acute hypoxia.

When patients with obstructive lung disease breathe helium-oxygen mixtures, their arterial PCO2, is lowered towards normal, indicating more effective ventilation. However, there is a lack of detailed respiratory data from clinical cases, so that the mechanisms remain unclear. To study relevant variables during hypoxemia and obstruction in the absence of disease, we undertook experiments with healthy subjects breathing normoxic and hypoxic gas mixtures of differing densities (air, 13.7% O2 in N2 and 13.7% O2 in helium) through an experimental obstruction (resistive airway loading). This increased airway resistance was twice that reported from the ambient-pleural pressure differences in patients with moderately severe emphysema. Without imposed resistance the total ventilation (VE) increased 27% on both hypoxic mixtures. With normoxia, the obstruction increased tidal volume but decreased frequency so that VE and alveolar ventilation (VA) were essentially unchanged. With hypoxia, breathing pattern changed similarly, but now VE decreased while VA was maintained. Helium returned the breathing patterns toward normal. Obstruction lowered the rapid increase in VE from two or three breaths of N2, but the decrease from two or three breaths of O2 was unchanged. We detected an increase in metabolic rate with obstructed breathing that was reduced by the helium mixtures. The remarkable finding was that despite the obstruction being markedly uncomfortable because of the high resistance, we did not find any substantial disturbance in gas exchange, compared to hypoxia with no obstruction. Thus, the main mechanisms responsible for improved blood gases in patients breathing helium mixtures were outside the scope of our experiment and likely related to disease factors.

Effect of head-down tilt on brain water distribution.

Vascular and tissue fluid dynamics in the microgravity of space environments is commonly simulated by head-down tilt (HDT). Previous reports have indicated that intracranial pressure and extracranial vascular pressures increase during acute HDT and may cause cerebral edema. Tissue water changes within the cranium are detectable by T2 magnetic resonance imaging. We obtained T2 images of sagittal slices from five subjects while they were supine and during -13 degrees HDT using a 1.5-Tesla whole-body magnet. The analysis of difference images demonstrated that HDT leads to a 21% reduction of T2 in the subarachnoid cerebrospinal fluid (CSF) compartment and a 11% reduction in the eyes, which implies a reduction of water content; no increase in T2 was observed in other brain regions that have been associated with cerebral edema. These findings suggest that water leaves the CSF and ocular compartments by exudation as a result of increased transmural pressure causing water to leave the cranium via the spinal CSF compartment or the venous circulation.

The effects of low levels of CO2 on ventilation during rest and exercise.

BACKGROUND: Measurements of pulmonary gas exchange are especially sensitive to low levels of CO2 in the environment; this is an important consideration in measurements in enclosed spaces. METHODS: In order to determine the responses to these low levels, subjects were exposed in five studies to partial pressures of inspired CO2 (PICO2) of 5.7 and 7.5 mmHg for 30 min during basal conditions at rest and to 5.4, 9.4 and 15 mmHg during a progressive exercise to VO2max on a cycle ergometer. RESULTS: In the two resting studies, total pulmonary ventilation and alveolar ventilation were increased by 19% at 7.5 mmHg (1.1% sea level equivalent) and 10% at 5.4 mmHg (0.8% equivalent), with clear evidence of CO2 retention in both studies. During exercise at 15 mmHg the VO2max was reduced significantly by 13%, compared with air at about the same maximal ventilation, but VO2max was not reduced at 9.4 mmHg. A 6% decrease in VO2max at a PICO2 of 5.4 mmHg may have resulted from these subjects being less fit. The maximal CO2 output and respiratory exchange ratio in the three exercise studies was always lower with CO2 than corresponding air measurements, indicating CO2 storage. Evaluation of submaximal measurements provided an equation for predicting ventilation as a function of PICO2 and VO2/VO2max and demonstrated that ventilation during submaximal exercise is increased significantly by the lowest CO2 level. BP and heart rate responses during submaximal and maximal work were not predictably altered by CO2 at these levels. CONCLUSION: These studies demonstrate that minimal CO2 levels have significant influences on pulmonary ventilation during rest and exercise and must be considered in acute studies in confined spaces such as space cabins. The inspired CO2 should be stated when ventilation measurements are reported under these conditions.

Ventilation during simulated altitude, normobaric hypoxia and normoxic hypobaria.

To investigate the possible effect of hypobaria on ventilation (VE) at high altitude, we exposed nine men to three conditions for 10 h in a chamber on separate occasions at least 1 week apart. These three conditions were: altitude (PB = 432, FIO2 = 0.207), normobaric hypoxia (PB = 614, FIO2 = 0.142) and normoxic hypobaria (PB = 434, FIO2 = 0.296). In addition, post-test measurements were made 2 h after returning to ambient conditions at normobaric normoxia (PB = 636, FIO2 = 0.204). In the first hour of exposure VE was increased similarly by altitude and normobaric hypoxia. The was 38% above post-test values and end-tidal CO2 (PET(CO2) was lower by 4 mmHg. After 3, 6 and 9 h, the average VE in normobaric hypoxia was 26% higher than at altitude (p < 0.01), resulting primarily from a decline in VE at altitude. The difference between altitude and normobaric hypoxia was greatest at 3 h (+ 39%). In spite of the higher VE during normobaric hypoxia, the PET(CO2) was higher than at altitude. Changes in VE and PET(CO2) in normoxic hypobaria were minimal relative to normobaric normoxia post-test measurements. One possible explanation for the lower VE at altitude is that CO2 elimination is relatively less at altitude because of a reduction in inspired gas density compared to normobaric hypoxia; this may reduce the work of breathing or alveolar deadspace. The greater VE during the first hour at altitude, relative to subsequent measurements, may be related to the appearance of microbubbles in the pulmonary circulation acting to transiently worsen matching. Results indicate that hypobaria per se effects ventilation under altitude conditions.

Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia.

Acute mountain sickness (AMS) strikes those in the mountains who go too high too fast. Although AMS has been long assumed to be due solely to the hypoxia of high altitude, recent evidence suggests that hypobaria may also make a significant contribution to the pathophysiology of AMS. We studied nine healthy men exposed to simulated altitude, normobaric hypoxia, and normoxic hypobaria in an environmental chamber for 9 h on separate occasions. To simulate altitude, the barometric pressure was lowered to 432 +/- 2 (SE) mmHg (simulated terrestrial altitude 4,564 m). Normobaric hypoxia resulted from adding nitrogen to the chamber (maintained near normobaric conditions) to match the inspired PO2 of the altitude exposure. By lowering the barometric pressure and adding oxygen, we achieved normoxic hypobaria with the same inspired PO2 as in our laboratory at normal pressure. AMS symptom scores (average scores from 6 and 9 h of exposure) were higher during simulated altitude (3.7 +/- 0.8) compared with either normobaric hypoxia (2.0 +/- 0.8; P < 0.01) or normoxic hypobaria (0.4 +/- 0.2; P < 0.01). In conclusion, simulated altitude induces AMS to a greater extent than does either normobaric hypoxia or normoxic hypobaria, although normobaric hypoxia induced some AMS.

Acute ventilatory response to simulated altitude, normobaric hypoxia, and hypobaria.

BACKGROUND: Some reports claim that ventilation (VE) is greater in human subjects in normobaric hypoxia than at altitude following an equivalent drop in inspired PO2 (PIO2). It has been suggested that reduced barometric pressure (PB) may decrease chemoreceptor sensitivity and account for these results. In this pilot study we tested the hypothesis that VE and hypoxic chemoresponsiveness would not be different after 30 min of normobaric hypoxia and altitude. METHODS: We exposed three male and three female subjects to four conditions in an environmental chamber, varying the order. The four conditions were: air (PB = 640, FIO2 = 0.204), hypobaria (434, 0.298), hypoxia (640, 0.141) and altitude (434, 0.203). We measured VE, end-tidal O2 and CO2 and arterial O2 saturation (SpO2) after 30 min in each environment, and while breathing 100% O2 for 1 min immediately thereafter. RESULTS: The mean increase in VE relative to air was 14%, 20% and 26% for hypobaria, hypoxia and altitude, respectively, with corresponding reductions in PETCO2 in the three conditions. The reduction in VE with 100% O2 was inversely proportional to the rise in SpO2 in all cases, indicating that chemoresponsiveness was unchanged by PB. When hypobaria preceded altitude, the VE at altitude increased less, relative to air, than when altitude was given first (not significant). CONCLUSIONS: The VE and chemosensitivity are about the same after 30 min of altitude and equivalent hypoxia. However, when the drop in PIO2 is not synchronous with the drop in PB, like at altitude, the VE values may be altered. Air density, hypoxic pulmonary vasoconstriction and circulating microbubbles may interact to account for the observed findings.

Acute effects of head-down tilt and hypoxia on modulators of fluid homeostasis.

In an effort to understand the interaction between acute postural fluid shifts and hypoxia on hormonal regulation of fluid homeostasis, the authors measured the responses to head-down tilt with and without acute exposure to normobaric hypoxia. Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), plasma aldosterone (ALD), and plasma renin activity (PRA) were measured in six healthy male volunteers who were exposed to a head-down tilt protocol during normoxia and hypoxia. The tilt protocol consisted of a 17 degrees head-up phase (30 minutes), a 28 degrees head-down phase (1 hour), and a 17 degrees head-up recovery period (2 hours, with the last hour normoxic in both experiments). Altitude equivalent to 14,828 ft was simulated by having the subjects breathe an inspired gas mixture with 13.9% oxygen. The results indicate that the postural fluid redistribution associated with a 60-minute head-down tilt induces the release of ANP and cGMP during both hypoxia and normoxia. Hypoxia increased cGMP, cAMP, ALD, and PRA throughout the protocol and significantly potentiated the increase in cGMP during head-down tilt. Hypoxia had no overall effect on the release of ANP, but appeared to attenuate the increase with head-down tilt. This study describes the acute effects of hypoxia on the endocrine response during fluid redistribution and suggests that the magnitude, but not the direction, of these changes with posture is affected by hypoxia.

Relationship between whole blood base excess and CO2 content in vivo.

Empirical relationships are demonstrated for whole blood base excess (BE) and CO2 content (CCO2), both calculated from in vivo measurements of PCO2, pH, hemoglobin concentration and O2 saturation. Comparisons are provided by measurements from three separate studies: (1) supine exercise (arterial and mixed venous samples); (2) chronic obstructive disease patients (arterial samples) breathing air and 100% O2; and (3) maximal seated exercise on a bicycle ergometer with and without added inspired CO2 (arterial samples before, during and after). Two standardized values of CCO2 (vol.%) are derived which closely relate to BE (mmol/l). The CCO2 at a PCO2 of 40 mmHG [CCO2(40)] for all samples (n = 220) demonstrated a curvilinear relationship: CCO2 (40) = 45.37 + 1.48(BE) + 0.0156(BE)2, r = + 0.996, SEE = 0.88 vol.%. The CCO2 at a pH of 7.4 [CCO2(7.4)] gave a linear relationship: CCO2(7.4) = 45.09 + 2.58(BE), r = + 0.998, SEE = 1.19 vol.%. Empirical computations for the Haldane factor from studies 1 and 2 gave values of 0.285 in terms of CCO2 (vol.%/vol.%) and 0.266 for BE (mmol/l/mmol reduced Hb). The BE values can serve as useful estimates of lactate concentrations during exercise and the excellent relationships between standardized CCO2 and BE demonstrate their equivalency and either can be utilized, depending on whether quantification of the CO2 dissociation curve or acid-base status is desired.

Effects of prolonged head-down bed rest on physiological responses to moderate hypoxia.

To determine the effects of hypoxia on physiological responses to simulated zero-gravity, cardiopulmonary and fluid balance measurements were made in 6 subjects (acclimatized to 5,400 ft) before and during 5 degrees head-down bed rest (HDBR) over 8 d at 10,678 ft and a second time at this altitude as controls (CON). The VO2max increased by 9% after CON, but fell 3% after HDBR (p < 0.05). This reduction in work capacity during HDBR could be accounted for by inactivity. The heart rate response to a head-up tilt was greatly enhanced following HDBR, while mean blood pressure was lower. No significant negative impact of HDBR was noted on the ability to acclimatize to hypoxia in terms of pulmonary mechanics, gas exchange, circulatory or mental function measurements. No evidence of pulmonary interstitial edema or congestion was noted during HDBR at the lower PIO2 and blood rheology properties were not negatively altered. Symptoms of altitude illness were more prevalent, but not marked, during HDBR and arterial blood gases and oxygenation were not seriously effected by simulated microgravity. Declines in base excess with altitude were similar in both conditions. The study demonstrated a minimal effect of HDBR on the ability to adjust to this level of hypoxia.

Alveolar ventilation to perfusion heterogeneity and diffusion impairment in a mathematical model of gas exchange.

This study describes a two-compartment model of pulmonary gas exchange in which alveolar ventilation to perfusion (VA/Q) heterogeneity and impairment of pulmonary diffusing capacity (D) are simultaneously taken into account. The mathematical model uses as input data measurements usually obtained in the lung function laboratory. It consists of two compartments and an anatomical shunt. Each compartment receives fractions of alveolar ventilation and blood flow. Mass balance equations and integration of Fick's law of diffusion are used to compute alveolar and blood O2 and CO2 values compatible with input O2 uptake and CO2 elimination. Two applications are presented. The first is a method to partition O2 and CO2 alveolar-arterial gradients into VA/Q and D components. The technique is evaluated in data of patients with chronic obstructive pulmonary disease (COPD). The second is a theoretical analysis of the effects of blood flow variation in alveolar and blood O2 partial pressures. The results show the importance of simultaneous consideration of D to estimate VA/Q heterogeneity in patients with diffusion impairment. This factor plays an increasing role in gas alveolar-arterial gradients as severity of COPD increases. Association of VA/Q heterogeneity and D may produce an increase of O2 arterial pressure with decreasing QT which would not be observed if only D were considered. We conclude that the presented computer model is a useful tool for description and interpretation of data from COPD patients and for performing theoretical analysis of variables involved in the gas exchange process.

Body fluid alterations during head-down bed rest in men at moderate altitude.

To determine the effects of hypoxia on fluid balance responses to simulated zero-gravity, measurements were made in six subjects (acclimatized to 5,400 ft; 1,646 m) before and during -5 degrees continuous head-down bed rest (HDBR) over 8 d at 10,678 ft. The same subjects were studied again at this altitude without HDBR as a control (CON) using a cross-over design. During this time, they maintained normal upright day-time activities, sleeping in the horizontal position at night. Fluid balance changes during HDBR in hypoxia were more pronounced than similar measurements previously reported from HDBR studies at sea level. Plasma volume loss (-19% on day 6) was slightly greater and the diuresis and natriuresis were doubled in magnitude as compared to previous studies in normoxia and sustained for 4 d during hypoxia. These changes were associated with an immediate, but transient rise in plasma atrial natriuretic peptide (ANP) to day 4 of 140% in HDBR and 41% in CON (p < 0.005), followed by a decline towards baseline. Differences were less striking between HDBR and CON for plasma antidiuretic hormone and aldosterone, which were transiently reduced by HDBR. Plasma catecholamines showed a similar pattern to ANP (+122%) in both HDBR and CON, suggesting that elevated ANP and catecholamines together accounted for the enhanced fluid shifts with HDBR during hypoxia.

Effects of acid-base status on acute hypoxic pulmonary vasoconstriction and gas exchange.

To investigate the relationship between hypoxic pulmonary vasoconstriction and respiratory and metabolic acidosis and respiratory alkalosis, the pulmonary gas exchange and pulmonary hemodynamic responses were measured in anesthetized, paralyzed, and mechanically ventilated dogs in two sets of experiments (series A, n = 6; series B, n = 10). The animals were treated with acute hypoxia, CO2 inhalation, hyperventilation, and dinitrophenol in various combinations. Multiple regression analysis indicated that mean pulmonary arterial pressure (Ppa) was significantly correlated with end-tidal PO2, mixed venous PO2, and the mean pulmonary capillary pH (average of arterial and mixed venous pH) as independent variables [series A: r = +0.999, standard error of estimate (SEE) = 0.4 mmHg; series B: r = +0.98, SEE = 1.4 mmHg]. Similar analyses of mean values published by other authors from an acute study on humans with exercise at sea level and simulated altitudes of 10,000 and 15,000 ft also indicated a good relationship (n = 14, r = +0.98, SEE = 2.1 mmHg). The mean data (n = 19) obtained in Operation Everest II at various exercise loads and simulated altitudes gave a correlation of r = +0.87, SEE = 6.1 mmHg. These empirical analyses suggest that variations in the rise of Ppa with hypoxia can be accounted for in vivo by the superimposed acid-base status. Furthermore, ventilation-perfusion inhomogeneity, as estimated in the dogs from end-tidal and arterial O2 and CO2 differences and assuming no true shunt or diffusion impairment, was highly correlated with Ppa and mean pulmonary capillary pH (r = +0.999 in series A, r = +0.77 in series B). The human data from the above studies also showed significant correlations between Ppa and directly measured ventilation-perfusion (standard deviation of perfusion obtained from inert gas measurements). These observations indicate that the beneficial effects of hyperventilation during hypoxia may be related to the marked alkalosis that serves to reduce Ppa and improve pulmonary gas exchange efficiency.

Cardiopulmonary responses to acute hypoxia, head-down tilt and fluid loading in anesthetized dogs.

The separate and combined acute effects of hypoxia (HY-11% O2), head-down tilt (HD-30 degrees) and fluid loading (FL-1.0 L saline) on hemodynamics and pulmonary gas exchange were determined in 17 anesthetized, mechanically ventilated dogs. Both during HY and normoxia (NO), the total respiratory compliance was decreased by HD, attributable to pulmonary vascular congestion. The reductions in compliance were twice as great with FL, indicating pulmonary interstitial edema, which was supported by histological observation of lung tissue. Pressure-flow relationships in the pulmonary circulation indicated that superimposing HD on HY doubled the increase in vascular resistance due to HY alone, while in the systemic circulation the resistance was returned to below NO by HD. A significant positive correlation between the changes in blood volume and pulmonary artery pressure for experimental transitions suggests that a shift in blood volume from systemic to pulmonary circulations and changes in total blood volume probably contributed substantially to these apparent changes in resistance. Pulmonary gas exchange efficiency, whether expressed in terms of shunt or ventilation/perfusion distribution from arterial-end-tidal PCO2 and PO2 differences, showed a significant inverse relationship with pulmonary driving pressure for the experimental conditions imposed. No clear synergistic effects of HY on HD were evident in contributing to pulmonary edema when superimposed prior to FL, but after FL this risk must be considered.