Respiratory, circulatory and neuropsychological responses to acute hypoxia in acclimatized and non-acclimatized subjects

Respiratory, circulatory and neuropsychological responses to stepwise, acute exposure at rest to simulated altitude (6,000 m) were compared in ten acclimatized recumbent mountaineers 24 days, SD 11 after descending from Himalayan altitudes of at least 4,000 m with those found in ten non-acclimatized recumbent volunteers. The results showed that hypoxic hyperpnoea and O2 consumption at high altitudes were significantly lower in the mountaineers, their alveolar gases being, however, similar to those of the control group. In the acclimatized subjects the activation of the cardiovascular system was less marked, systolic blood pressure, pulse pressure, heart rate and thus (calculated) cardiac output being always lower than in the controls; diastolic blood pressure and peripheral vascular resistance, however, were maintained throughout in contrast to the vasomotor depression induced by central hypoxia which occurred in the non-acclimatized subjects at and above 4,000 m [alveolar partial pressure of O2 less than 55-50 mmHg (7.3-6.6 kPa)]. It was concluded that in the acclimatized subjects at high altitude arterial vasodilatation and neurobehavioural impairment, which in the non-acclimatized subjects reflect hypoxia of the central nervous system, were prevented; that acclimatization to high altitude resulted in a significant improvement of respiratory efficiency and cardiac economy, and that maintaining diastolic blood pressure (arterial resistance) at and above 4,000 m may represent a useful criterion for assessing hypoxia acclimatization.     

Ventilatory, circulatory, endocrine, and renal effects of almitrine infusion in man: a contribution to high altitude physiology

Diuresis at altitude was thought to be the result of chemoreceptor stimulation leading to a reduction of cardiac volume overload. This hypothesis was tested in ten young, healthy subjects by infusion of almitrine (0.5 mg.kg-1 body mass within 30 min) assuming analogous sites of action, i.e. arterial chemoreceptors and pulmonary vessels, for almitrine as for hypoxic hypoxia. The results show that almitrine increases ventilation, heart rate, systolic blood pressure, central venous pressure and natriuresis, but fails to increase significantly atrial natriuretic peptide plasma concentration and diuresis. It is concluded: (1) that almitrine has similar sites of action as hypoxic hypoxia at about 5000 m, (2) that natriuresis during arterial chemoreceptor stimulation might reduce cardiac volume overload, (3) that the volume excretion hypothesis, in particular the pathways from the cardiac volume overload to the water diuresis, need, for an understanding of the hypoxia-induced diuresis, further direct investigations at altitude.     

Acclimatization to hypoxia modulates the tryptophan 2,3-dioxygenase activity in rats exposed to simulated high altitude.

1. Exposure of rats to an 8000 m altitude increased the hepatic tryptophan 2,3-dioxygenase (EC 1.13.1.12) activity. 2. Acclimatization to hypoxia by a repeated exposure to an altitude of 5000 m induced a marked decrease in liver tryptophan dioxygenase activity after the rats were subjected to an 8000 m altitude, but a pre-exposure to 4000 m altitude showed no effect on the enzyme activity. 3. Plasma tryptophan was rapidly decreased by exposure to 8000 m altitude to the same extent in the acclimatized and non-acclimatized rats. 4. Plasma tryptophan may be utilized as the substrate for tryptophan dioxygenase in liver of the non-acclimatized rats under highly hypoxic conditions; however, acclimatized rats can reserve tryptophan as the substrate for the alternative metabolism other than the degradation pathway in liver.     

Increased affinity to substrate in sarcolemmal ATPases from hearts acclimatized to high altitude hypoxia

It has been well documented that acclimatization to chronic high altitude hypoxia involves a complex of adaptation changes which are capable of protecting the myocardium in diverse situations such as in acute hypoxia, coronary occlusion-induced ischaemia or isoprenaline-induced calcium overload. Since many of the former changes concern membrane functions, namely those of the sarcolemma, the activities and kinetic properties of sarcolemmal Mg2+-, Ca2+- and (Na+ + K+)-ATPase were investigated in right heart ventricles of rats acclimatized to intermittent high altitude hypoxia simulated in a barochamber. In the course of the experiment, the ventricles were subjected to a special anoxic test in vitro. The high altitude induced increase in cardiac tolerance to anoxia was not accompanied by any preservation of the sarcolemmal ATPase activities. On the contrary, membrane preparations obtained from the right ventricles of hearts acclimatized to high altitude exhibited significantly lower ATPase activities in comparison to non-acclimatized controls. The significant diminution in Km values of ATPases established in acclimatized hearts points to an increase in the affinity of their active sites to ATP. The latter effect is in agreement with the lowered rate of both the decrease in ATPase activities and the reduction of contractility in acclimatized hearts during the anoxic test, as well as with the considerably improved postanoxic reparability of contractions as compared to the controls. It is being concluded that the sarcolemmal changes at the level of ATPases involved in ionic transport processes represent an integral part of the adaptation complex to chronic high altitude hypoxia.     

Ventilatory and cardiac responses to hypoxia at submaximal exercise are independent of altitude and exercise intensity

The hypoxic exercise test combining a 4,800-m simulated altitude and a cycloergometer exercise at 30% of normoxic maximal aerobic power (MAP) is used to evaluate the individual chemosensitivity to hypoxia in submaximal exercise conditions. This test allows the calculation of three main parameters: the decrease in arterial oxygen saturation induced by hypoxia at exercise (ΔSa(e)) and the ventilatory (HVR(e)) and cardiac (HCR(e)) responses to hypoxia at exercise. The aim of this study was to determine the influence of altitude and exercise intensity on the values of ΔSa(e), HVR(e), and HCR(e). Nine subjects performed hypoxic tests at three simulated altitudes (3,000 m, 4,000 m, and 4,800 m) and three exercise intensities (20%, 30%, and 40% MAP). ΔSa(e) increased with altitude and was higher for 40% MAP than for 20% or 30% (P < 0.05). For a constant heart rate, the loss in power output induced by hypoxia, relative to ΔSa(e), was independent of altitude (4,000-4,800 m) and of exercise intensity. HVR(e) and HCR(e) were independent of altitude (3,000-4,800 m) and exercise intensity (20%-40% MAP). Moreover, the intraindividual variability of responses to hypoxia was lower during moderate exercise than at rest (P < 0.05 to P < 0.001). Therefore, we suggest that HVR(e) and HCR(e) are invariant parameters that can be considered as intrinsic physiological characteristics of chemosensitivity to hypoxia.     

Interaction between cold and altitude exposure on pulmonary circulation of cattle

Hereford calves were exposed in a temperature-controlled hypobaric chamber to environmental temperatures of -2 to 1 degree C (cold) at altitudes of 1,524 m (resident altitude) and 3,048 m 1) to characterize the effects of cold exposure on the pulmonary circulation; 2) to examine the role of cold-induced hypoventilation on the pulmonary circulation; and 3) to examine the interaction between cold and hypoxia on the pulmonary circulation. Cold exposure produced a significant increase in pulmonary arterial pressure (Ppa), pulmonary arterial wedge pressure (Ppaw), and pulmonary vascular resistance (PVR) at both 1,524 and 3,048 m without affecting cardiac output. Concomitantly, cold exposure caused reductions in minute ventilation, respiratory rate, end-tidal O2 tension (PETO2), and arterial O2 tension (PaO2). Tidal volume, end-tidal CO2 tension, and arterial CO2 tension increased. Neither arterial pH nor O2 consumption changed during cold exposure. These results indicated that both pulmonary arterial and venous vasoconstriction were responsible for the pulmonary hypertension associated with cold exposure. Acute exposure to 3,048 m during cold exposure produced increases in Ppa and PVR that were similar to those elicited by cold exposure at 1,524. It was concluded that altitude exposure neither attenuated nor potentiated the effect of cold exposure on the pulmonary circulation; rather, altitude and cold exposure interacted additively. O2 administered during cold exposure to restore PETO2 and PaO2 to control values partially restored Ppa and PVR to control values. This suggested that a portion of the pulmonary hypertension associated with cold exposure was due to hypoxic pulmonary vasoconstriction elicited by the cold-induced alveolar hypoventilation.     

Normotensive normoxic men undergoing water diuresis fail to respond to stimulation of their peripheral arterial chemoreceptors by almitrine with an increase in plasma concentrations of atrial natriuretic factor

The purpose of this study was to investigate the possible participation of atrial natriuretic factor (ANF) in the natriuretic and diuretic response occurring after stimulation of the peripheral arterial chemoreceptors by almitrine bismesylate in normoxic humans. The experiments were performed in 14 healthy male volunteers undergoing water diuresis. Each subject participated in two experiments. In one of them they ingested 100-mg almitrine at 12 p.m. The other study served as a control. Surprisingly, our subjects responded to almitrine with an elevation of urine flow only, whereas sodium excretion remained almost unchanged over the whole period of the experiments. As regards ANF plasma concentrations, no statistically significant differences between the control and the almitrine group could be observed. Moreover, no direct connection between ANF plasma concentrations and renal volume excretion was detectable. We conclude that a specific stimulation of peripheral arterial chemoreceptors by almitrine in humans undergoing water diuresis did not seem to raise ANF plasma concentrations as is the case at high altitude. Therefore we would suggest that there exists no specific reflex influence of these receptors on ANF release.     

Chemoreceptor sensitivity and maladaptation to high altitude in man

Studies were carried out to find out the role of chemoreceptor sensitivity in the causation of maladaptation syndromes on acute exposure to altitude. The experiments were done in two phases. In phase I, the responses in chemoreceptor sensitivity were studied in altitude acclimatized subjects and compared with those who suffered from either High Altitude Pulmonary Oedema (HAPO) or Acute Mountain Sickness (AMS). In Phase II, a similar comparison was done in two groups of subjects, one representing normal sojourners at 3,500 m and the other being subjects who had just recovered from HAPO. The first phase was done at Delhi; and the second at an altitude of 3,500 m. Parameters of assessment were hypoxic sensitivity, carbon dioxide sensitivity, ventilation (VE), respiratory frequency (Rf), forced vital capacity (FVC), forced expiratory volume at the first second (FEV1), heart rate (HR), blood pressure (BP), and oral temperature (Tor). The results showed significantly lower sensitivity to both hypoxia and carbon dioxide in maladapted subjects, as compared to those who were acclimatized in both the categories suggesting thereby that reduced chemoreceptor sensitivity might be an initiating factor in the causation of maladaptation syndromes at altitude.     

Mitochondrial DNA mutations contribute to high altitude pulmonary edema via increased oxidative stress and metabolic reprogramming during hypobaric hypoxia

High altitude pulmonary edema (HAPE) is experienced by non-acclimatized sea level individuals on exposure to high altitude hypoxic conditions. Available evidence suggests that genetic factors and perturbed mitochondrial redox status may play an important role in HAPE pathophysiology. However, the precise mechanism has not been fully understood. In the present study, sequencing of mitochondrial DNA (mtDNA) from HAPE subjects and acclimatized controls was performed to identify pathogenic mutations and to determine their role in HAPE. Hypobaric hypoxia induced oxidative stress and metabolic alterations were also assessed in HAPE subjects. mtDNA copy number, mitochondrial oxidative phosphorylation (mtOXPHOS) activity, mitochondrial biogenesis were measured to determine mitochondrial functions. The data revealed that the mutations in Complex I genes affects the secondary structure of protein in HAPE subjects. Further, increased oxidative stress during hypobaric hypoxia, reduced mitochondrial biogenesis and mtOXPHOS activity induced metabolic reprogramming appears to contribute to mitochondrial dysfunctions in HAPE individuals. Haplogroup analysis suggests that mtDNA haplogroup H2a2a1 has potential contribution in the pathobiology of HAPE in lowlanders. This study also suggests contribution of altered mitochondrial functions in HAPE susceptibility.     

Effects of atropine and propranolol on the respiratory, circulatory, and ECG responses to high altitude in man

In order to analyze the respiratory, cardiovascular, and ECG responses to acute hypoxic hypoxia, three experimental series were carried out in a randomized manner on 11 healthy, unacclimatized volunteers at rest during standardized stepwise exposure to 6000 m (PAO2 35.2 +/- 2.9 mmHg/4.7 +/- 0.4 kPa) in a low-pressure chamber a) without (control), b) with propranolol, and c) with atropine combined with propranolol. The results show that hypoxic hyperventilation and alveolar gases are not affected by activation of the sympatho-adrenal axis or by parasympathetic withdrawal. Sympathetic activity, however, increases heart rate, stroke volume (pulse pressure), estimated cardiac output and systolic blood pressure, whereas decreased parasympathetic activity increases heart rate and estimated cardiac output, but lowers stroke volume. The fall in peripheral resistance, observed during progressive hypoxia in all three groups, is thought to be due to hypoxia-induced depression of the vasomotor center. At altitude catecholamine secretion and vagal withdrawal synergistically account in the ECG for the R-R shortening, the relative Q-T lengthening, the elevation of the P wave and the ST-T flattening. Probable direct hypoxic effects on the heart are the increase in P-Q duration and the minor but still significant depression of the T wave. It is concluded that at altitude increased sympatho-adrenal and decreased parasympathetic activity is without effect on hypoxic hyperventilation, but accounts for most of the cardiovascular and ECG changes. Diminution of sympathetic activity and imminent vagotonia arising after acute ascent to 6000 m probably reflect hypoxia of the central nervous system.     

Renal adrenomedullin and high altitude diuresis

Previous investigations revealed that most of the fluid regulating hormones showed no consistent relationship to the hypoxic diuretic response (HDR). In this study we examined if adrenomedullin (AM), a hypoxia-mediated diuretic/natriuretic peptide is connected to HDR. Thirty-three persons were examined at low altitude (LA), on the third exposure day at 3440 m (medium altitude, MA) and on the fourteenth day at 5050 m (high altitude, HA). Nocturnal diuresis rose from 460 ml [interquartile range 302 ml] at LA to 560 [660] ml at MA to 1015 [750] ml at HA (p<0.005). Sodium excretion was similar at LA and MA (41.8 [27.0] vs. 41.4 [28.4] mM) and increased to 80.2 [29.1] mM at HA (p<0.005). Urinary AM excretion was 7.9 [3.9] at LA, 7.5 [5.7] pM at MA, and increased to 10.5 [5.1] pM (p<0.05) at HA. Urinary AM excretion was correlated to diuresis (r=0.72, p<0.005) and sodium excretion (r=0.57, p<0.005). Plasma AM concentration rose from 16.4 [3.1] to 18.8 [4.9] pM/l at MA (p<0.005) and to 18.3 [4.3] pM/l at HA (p<0.005). Plasma AM concentration and urinary AM excretion were not correlated, neither were plasma AM concentration and diuresis or natriuresis. Our data suggest the involvement of increased renal AM production in the pathophysiology of high altitude fluid and sodium loss.     

Age-dependent influence of a moderate altitude (1,350 m) on the rat cardiopulmonary system

The aim of the study was to determine whether a moderate altitude (1,350 m, Strbské Pleso, High Tatras) would act as a hypoxic stimulus on the cardiopulmonary system of young and adult rats. We used three experimental groups of animals differing in the duration of time for which they were kept at the given altitude (60 and 120 days) and the age at which they were acclimatized (from the 5th and the 60th day of life). The controls were kept at an altitude of 200 m (Prague). We found that an altitude of 1,350 m produced a significant increase in blood pressure in the lesser circulation; this response did not depend on the animals' age. Right ventricular enlargement occurred at the same time and was more pronounced in rats which had been acclimatized from infancy. The systemic blood pressure fell mildly, but significantly, only in animals exposed to altitude from adulthood; elevation of the haematocrit was likewise recorded only in this group. The results show that even a moderate altitude influences the cardiopulmonary system of the rat in a manner characteristic of the effect of chronic hypoxic hypoxia.     

The ECG changes due to altitude and to catecholamines

In order to distinguish the effects of beta-receptor stimulation on the ECG from other factors during short-term adjustment to hypoxic aerohypoxia, the ECG of 19 volunteers were compared during moderately acute, stepwise exposure to high altitude (6,000 m) in a low pressure chamber, once with and once without beta-receptor blockade (propranolol), and after isoprenaline inhalation at ground level. The results show that beta-receptor stimulation accounts mainly for most ECG changes during altitude exposure, i.e., for the shortening of R-R interval, the lengthening of Q-T and in particular for the ST-T flattening, the latter therefore being only an indirect sign of hypoxia. After exclusion of the catecholamines, the minor but still significant ECG changes at altitude (shortening of R-R interval, increase of P wave, prolongation of P-Q, deviation of the R vector, T wave flattening in the left precordial leads) may be attributed to other, so far undefined factors, such as cardiac hypoxia, vagal withdrawal, or increase of pulmonary resistance.     

Effects of high altitude and water deprivation on arginine vasopressin release in men

High-altitude exposure changes the distribution of body water and electrolytes. Arginine vasopressin (AVP) may influence these alterations. The purpose of this study was to examine the effect of a 24-h water deprivation trial (WDT) on AVP release after differing altitude exposures. Seven healthy males (age 22 +/- 1 yr, height 176 +/- 2 cm, mass 75.3 +/- 1.8 kg) completed three WDTs: at sea level (SL), after acute altitude exposure (2 days) to 4,300 m (AA), and after prolonged altitude exposure (20 days) to 4,300 m (PA). Body mass, standing and supine blood pressures, plasma osmolality (Posm), and plasma AVP (PAVP) were measured at 0, 12, 16, and 24 h of each WDT. Urine volume was measured at each void throughout testing. Baseline Posm increased from SL to altitude (SL 291.7 +/- 0.8 mosmol/kgH2O, AA 299.6 +/- 2.2 mosmol/kgH2O, PA 302.3 +/- 1.5 mosmol/kgH2O, P < 0.05); however, baseline PAVP measurements were similar. Despite similar Posm values, the maximal PAVP response during the WDT (at 16 h) was greater at altitude than at SL (SL 1.7 +/- 0.5 pg/ml, AA 6.4 +/- 0.7 pg/ml, PA 8.7 +/- 0.9 pg/ml, P < 0.05). In conclusion, hypoxia appeared to alter AVP regulation by raising the osmotic threshold and increasing AVP responsiveness above that threshold.     

Effect of acute exposure to 3660 m altitude on orthostatic responses and tolerance.

Orthostatic reflexes were examined at 375 m and after 60 min of exposure in a hypobaric chamber at 3660 m using a 20-min 70 degrees head-up tilt (HUT) test. Mean arterial blood pressure, R wave-R wave interval (RRI), and mean cerebral blood flow velocity (MFV) were examined with coarse-graining spectral analysis. Of 14 subjects, 7 at 375 m and 12 at 3660 m were presyncopal. Immediately on arrival to high altitude, breathing frequency and MFV increased, and endtidal PCO2, RRI, RRI complexity, and the parasympathetic nervous system indicator decreased. MFV was similar in HUT at both altitudes. The sympathetic nervous system indicator increased with tilt at 3660 m, whereas parasympathetic nervous system indicator decreased with tilt at both altitudes. Multiple regression analysis of supine variables from either 375 or 3660 m and the time to presyncope at 3660 m indicated that, after 1 h of exposure, increased presyncope at altitude was the result of 1). ineffective peripheral vasoconstriction, despite increased cardiac sympathetic nervous system activity with HUT, and 2). insufficient cerebral perfusion owing to cerebral vasoconstriction as the result of hypoxic hyperventilation-induced hypocapnia.     

Epidermal transpiration, ultrastructural characteristics and net photosynthesis of white spruce somatic seedlings in response to in vitro acclimatization

Mortality of transplanted somatic seedlings at the stage of acclimatization is often high and likely due to rapid change in environmental conditions. To investigate the potential of in vitro acclimatization of somatic seedlings before soil transfer, somatic seedlings of white spruce ( Picea glauca [Moench] Voss) were germinated on a liquid medium supplemented with sucrose. After 6 weeks in germination, sucrose was omitted from the medium for a supplementary 6 weeks at which time somatic seedlings were acclimatized in vitro in their germination tubes before transfer to soil. In vitro acclimatization of somatic seedlings was realized by transferring the test tubes containing the germinated somatic seedlings to the greenhouse for 9 days. During this period, the culture tube lids of acclimatized somatic seedlings were lifted progressively increasing air exchange between the tube and the greenhouse whereas, for non-acclimatized somatic seedlings the culture tubes were maintained closed during in vitro acclimatization. In vitro acclimatized somatic seedlings had higher asymptotic net photosynthesis ( P _n) at light saturation than non-acclimatized seedlings (6 versus 4.5 µmol m⁻² s⁻¹). At the end of the in vitro acclimatization period, a lower rate of epidermal transpiration was also observed for acclimatized somatic seedlings (3.85 versus 4.75% h⁻¹). Microscopic observations showed that starch granules were more abundant in needles of acclimatized somatic seedlings than in non-acclimatized somatic seedlings, probably as a result of their greater photosynthetic capacity. Needles from acclimatized somatic seedlings also showed more epicuticular wax projections than needles from non-acclimatized somatic seedlings. These structural changes may help somatic seedlings to restrict epidermal water loss and stomatal aperture.     

Balancing tissue perfusion demands: cardiovascular dynamics of Cancer magister during exposure to low salinity and hypoxia

Decapod crustaceans inhabit aquatic environments that are frequently subjected to changes in salinity and oxygen content. The physiological responses of decapod crustaceans to either salinity or hypoxia are well documented; however, there are many fewer reports on the physiological responses during exposure to these parameters in combination. We investigated the effects of simultaneous and sequential combinations of low salinity and hypoxia on the cardiovascular physiology of the Dungeness crab, Cancer magister. Heart rate, as well as haemolymph flow rates through the anterolateral, hepatic, sternal and posterior arteries were measured using a pulsed-Doppler flowmeter. Summation of flows allowed calculation of cardiac output and division of this by heart rate yielded stroke volume. When hypoxia and low salinity were encountered simultaneously, the observed changes in cardiac properties tended to be a mix of both factors. Hypoxia caused a bradycardia, whereas exposure to low salinity was associated with a tachycardia. However, the hypoxic conditions had the dominant effect on heart rate. Although hypoxia caused an increase in stroke volume of the heart, the low salinity had a more pronounced effect, causing an overall decrease in stroke volume. The patterns of haemolymph flow through the arterial system also varied when hypoxia and low salinity were offered together. The resulting responses were a mix of those resulting from exposure to either parameter alone. When low salinity and hypoxia were offered sequentially, the parameter experienced first tended to have the dominant effect on cardiac function and haemolymph flows. Low salinity exposure was associated with an increase in heart rate, a decrease in stroke volume and cardiac output, and a concomitant decrease in haemolymph flow rates. Subsequent exposure to hypoxic conditions caused a slight decrease in rate, but other cardiovascular variables were largely unaffected. In contrast, when low salinity followed acclimation to hypoxic conditions, apart from an increased heart rate, there were no other cardiovascular changes associated with the low salinity episode. The implications of these changes in cardiovascular dynamics are discussed in relation to physiological mechanisms and the ecology of decapod crustaceans, in hypoxic or low salinity environments.     

急性缺氧暴露不同时间家兔血浆心钠素、抗利尿激素、醛固酮的变化

本实验观察了８０只家兔在急性缺氧６、１２、２４、３６、４８、６０、７１ｈ后肺指数、血浆心钠素（ＡＮＰ）、抗利尿激素（ＡＶＰ）、醛固酮（ＡＬＤ）及尿量的变化。结果表明：在缺氧２４－７２ｈ,肺指数明显升高,尿量减少;缺氧１６ｈ,血浆ＡＮＰ明显升高;而缺氧４８和６０ｈ无ＡＮＰ升高现象。缺氧７２ｈ,血浆ＡＮＦ又明显高于缺氧前水平;血浆ＡＶＰ只在缺氧２４ｈ明显升高;血浆ＡＬＤ未见显著性变化。这些结果提示：在缺氧状态下,ＡＮＰ、ＡＶＰ的释放均与缺氧暴露的时间有关。这些激素的平衡失调可能与急性缺氧性肺水肿的发生有关。     

Arterial baroreceptors control plasma vasopressin responses to graded hypotension in conscious dogs

We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.     

Low acute hypoxic ventilatory response and hypoxic depression in acute altitude sickness

Persons with acute altitude sickness hypoventilate at high altitude compared with persons without symptoms. We hypothesized that their hypoventilation was due to low initial hypoxic ventilatory responsiveness, combined with subsequent blunting of ventilation by hypocapnia and/or prolonged hypoxia. To test this hypothesis, we compared eight subjects with histories of acute altitude sickness with four subjects who had been asymptomatic during prior altitude exposure. At a simulated altitude of 4,800 m, the eight susceptible subjects developed symptoms of altitude sickness and had lower minute ventilations and higher end-tidal PCO2's than the four asymptomatic subjects. In measurements made prior to altitude exposure, ventilatory responsiveness to acute hypoxia was reduced in symptomatic compared to asymptomatic subjects, both when measured under isocapnic and poikolocapnic (no added CO2) conditions. Diminution of the poikilocapnic relative to the isocapnic hypoxic response was similar in the two groups. Ventilation fell, and end-tidal PCO2 rose in both groups during 30 min of steady-state hypoxia relative to values observed acutely. After 4.5 h at 4,800 m, ventilation was lower than values observed acutely at the same arterial O2 saturation. The reduction in ventilation in relation to the hypoxemia present was greater in symptomatic than in asymptomatic persons. Thus the hypoventilation in symptomatic compared to asymptomatic subjects was attributable both to a lower acute hypoxic response and a subsequent greater blunting of ventilation at high altitude.