Hypoxic pulmonary steady-state diffusing capacity for CO and alveolar-arterial O2 pressure differences in growing rats after adaptation to a simulated altitude of 3500 m

Summary Steady-state pulmonary diffusing capacity for CO and alveolar-arterial O₂ pressure differences were measured at hypoxia in growing rats adapted to a simulated altitude of 3500 m. The pulmonary diffusing capacity was significantly higher and the alveolar-arterial gradients were significantly lower in the adapted animals as compared with the controls exposed to hypoxia for the first time. The increased diffusing capacity could be explained entirely by the increase of blood O₂ and CO capacity whereas the decrease of gradients might be explained by the increase of blood O₂ capacity together with an increase of the arterio-venous O₂ difference.     

Hypoxic pulmonary steady-state diffusing capacity for CO and cardiac output in rats born at a simulated altitude of 3500 m

Summary In rats born in the low pressure chamber from sea level parents a higher hypoxic steady-state pulmonary diffusing capacity for CO was found as compared with controls of similar body weight. This difference could be explained by a difference in age or by an increase of blood O₂ capacity. There was no difference in alveolar ventilation and alveolar-arterial O₂ pressure differences, a lower cardiac output, no difference in arterial O₂ tension, no difference in arterial O₂ content but a decreased mixed-venous O₂ content as compared with control rats measured at hypoxia. A shift of the standard blood O₂ dissociation curve to the right was found in the simulated high altitude exposed rats. Calculated mixed-venous O₂ pressure was not altered in these rats; since arterial O₂ pressure was the same no difference in mean tissue capillary O₂ pressure may be presumed as compared with control animals. The results suggest that the first generation of rats exposed to simulated high altitude for their whole life is not only less adapted than animals exposed in their youth (as described in previous work) but that the ability to promote the O₂ transport in time of need in rats born in the low pressure chamber is probably even inferior to that of the controls.     

Oxygen transport in guinea pigs native to high altitude (Junin,Peru, 4,105 m)

In guinea pigs native to high altitude in the Andes (Peru) the arterial and mixed-venousP _{O 2},P _{CO 2}, pH, and O₂ content were measured at high altitude during breathing ambient air.Identical measurements were done in Nijmegen, The Netherlands, on sea-level natives and on guinea pigs exposed for 4–5 weeks to simulated altitude in a low pressure chamber, while breathing ambient air (normoxia) or an hypoxic mixture of O₂ in N₂ with aP _{I O 2} similar to that of the ambient air at high altitude. A standard blood O₂ dissociation curve (ODC) was estimated in vitro (at pH=7.4 and 37.5°C), and a standard in vivo ODC was derived from measuredP _{O 2},S _{O 2} and pH in all three groups.Both guinea pigs native to natural or simulated high altitude had a higher hematocrit and blood O₂ capacity than sea-level controls. These increased altitude values were, however, almost the same as the sea-level values of man or rat. No difference in the ideal alveolararterialP _{O 2} difference or lung diffusing capacity for O₂ was found between (natural or simulated) high altitude animals and their corresponding controls, when measured at hypoxia. Mixed-venousP _{O 2} was higher in guinea pigs from the natural high altitude (but not in those from the low pressure chamber) when compared with control sea-level natives studied at hypoxia. No difference among groups in cardiac output was found, while breathing the same inspiratory mixture. In the guinea pigs native to high altitude a higher P₅₀ and a lower Hill numbern for the in vitro ODC were found when compared with the controls or with the guinea pigs exposed to simulated high altitude. This was not observed when the ODC's were estimated in vivo.The rather modest polycythemic response to high altitude in guinea pigs coincides with a low value of P₅₀, when related to body weight. In this respect the guinea pig seems to be more closely related to the typical high altitude mammals like Andean camelids and rodents than to man or rat that respond to high altitude with a pronounced polycythemia and possess a rather high P₅₀ with respect to body weight.All data obtained in Peru are part of the scientific material acquired during the Italian Lake Mountain Scientific Expedition to Peru, march and April 1978, under the direction of Prof. Dr. P. G. Data from the University of Chieti, Italy.Part of the results were presented at the 12. Atmungsphysiologische Arbeitstagung, Göttingen, FRG, January 26–27, 1979     

Methodische Untersuchungen zur polarographischen Messung der Atmung und des „kritischen Sauerstoffdrucks” bei Mitochondrien und isolierten Zellen mit der membranbedeckten Platinelektrode

Summary In growing rats adapted to a simulated altitude of 3500 m for about 4 weeks and in their controls the evolution of cardiac ventricular weight was followed. The increase of total ventricular weight found in the adapted animals can be attributed exclusively to the increase of right ventricular weight. In other adapted and control animals cardiac capillary densities, muscle fiber diameter and external capillary radius were estimated and fiber—capillary ratio and diffusion distance were calculated. There was an increase of capillary density together with a decrease of muscle fiber density, fiber-capillary ratio and diffusion distance in the right but not in the left ventricle of the adapted rats. The muscle fiber diameters, however, were larger in both heart ventricles of the rats exposed to a simulated high altitude, especially in the right ventricle. This indicates that true hypertrophy of the muscle fibers is mainly responsible for the increase of right ventricular weight. In the left ventricle, however, a hypertrophy of the muscle fibers together with a decrease of stroma components is demonstrated. The physiological importance of the shorter diffusion distance in the right ventricle of the high altitude adapted rats is discussed and it is suggested that the shorter diffusion distance may help to keep the tissue O₂ partial pressure above the critical value, mainly also in extreme situations with high myocardial O₂ consumption.     

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

Summary 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 < 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.Dedicated to Prof. A. Schreiber on the occasion of his 60th birthday     

During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory level.

To test the hypothesis that the increased sympathetic tonus elicited by chronic hypoxia is needed to match O(2) delivery with O(2) demand at the microvascular level eight male subjects were investigated at 4559 m altitude during maximal exercise with and without infusion of ATP (80 mug (kg body mass)(-1) min(-1)) into the right femoral artery. Compared to sea level peak leg vascular conductance was reduced by 39% at altitude. However, the infusion of ATP at altitude did not alter femoral vein blood flow (7.6 +/- 1.0 versus 7.9 +/- 1.0 l min(-1)) and femoral arterial oxygen delivery (1.2 +/- 0.2 versus 1.3 +/- 0.2 l min(-1); control and ATP, respectively). Despite the fact that with ATP mean arterial blood pressure decreased (106.9 +/- 14.2 versus 83.3 +/- 16.0 mmHg, P < 0.05), peak cardiac output remained unchanged. Arterial oxygen extraction fraction was reduced from 85.9 +/- 5.3 to 72.0 +/- 10.2% (P < 0.05), and the corresponding venous O(2) content was increased from 25.5 +/- 10.0 to 46.3 +/- 18.5 ml l(-1) (control and ATP, respectively, P < 0.05). With ATP, leg arterial-venous O(2) difference was decreased (P < 0.05) from 139.3 +/- 9.0 to 116.9 +/- 8.4(-1) and leg .VO(2max) was 20% lower compared to the control trial (1.1 +/- 0.2 versus 0.9 +/- 0.1 l min(-1)) (P = 0.069). In summary, at altitude, some degree of vasoconstriction is needed to match O(2) delivery with O(2) demand. Peak cardiac output at altitude is not limited by excessive mean arterial pressure. Exercising leg .VO(2peak) is not limited by restricted vasodilatation in the altitude-acclimatized human.     

Renal hemodynamics and renal O2 uptake during hypoxia in the anesthetized rabbit

Summary The effects of hypoxic hypoxia on renal hemodynamics and metabolism have been studied in anaesthetized mechanically ventilated rabbits. Acute hypoxia (F₁O₂=0.10,PaO₂=35 torr) induces at constant mean arterial pressure a 45% decrease in RBF, GFR, and whereas free water clearance increases. These alterations were still apparent 50 min after resuming normal arterial oxygenation. In order to assess the role of the stimulation of catecholamine release in these observations, two other sets of experiments were performed: 1) the animals were ventilated with the same hypoxic gas mixture but after adrenergic blockade (phentolamine: 0.2 mg·kg·min^–1 i.v.), 2) hypoxia was induced by ventilating the animals with CO (F_ICO=0.002) at constantPaO₂. Increase in renal vascular resistance and reduction of renal O₂ uptake were still observed. This indicates that adrenergic stimulation cannot fully explain the renal vasoconstriction encountered in hypoxia. The role of a local vasoactive factor, especially that of the renin angiotensin system is discussed. The apparent O₂ cost of Na reabsorption was not greatly modified by any type of hypoxia and the Na:O₂ ratio remained close to the value observed in normoxic animals. This indicates that the kidney may adapt to hypoxia by reducing its O₂ demand keeping unaltered its tubular function and basal O₂ needs.     

Resting values of left ventricular work to coronary blood flow ratio in rats exposed to intermittent high altitude hypoxia and swimming

Summary Total hemodynamic values and left ventricular blood flow were studied using Sapirstein's method of ⁸⁶Rb uptake in female rats 24 h after a last exposure to high altitude. A simulated altitude of 1350 m was used, initial exposure being for 30 min, gradually increased by 30 min daily up to 330 min daily for 5 days a week; the total number of exposures was 32. In another animal group the hypobaric exposure was combined with swimming in water at 37 C.In both experimental groups the cardiac output and stroke volume increased, and in rats undergoing swimming the total peripheral resistance decreased as well.In the rats exposed to intermittent hypoxia only, left ventricular blood flow increased by about the same proportion as the cardiac output. The ratio of left ventricular work to coronary blood flow was significantly increased.In rats exposed to the combined influence of hypoxia and swimming, the increase in left ventricular blood flow did not match either the increase in cardiac output, or the weight gain of the left ventricle. The ventricular work to coronary blod flow ratio was the same as in controls.     

Maternal O2 transport and fetal growth in Colorado,Peru, and Tibet high-altitude residents

Human populations have lived at high altitudes for lengths of time which are likely to be shortest in Colorado, intermediate in Peru, and longest in Tibet. We hypothesized that the longest-resident high-altitude populations have beccome better adapted than shorter-resident groups as a result of superior abilities to transport and/or utilize O₂. Because birth weights are reduced at high altitude and decreased birth weight is associated with increased infant mortality, our criterion for assessing adaptation was preservation of birth weights close to values associated with the lowest mortality risk. Colorado (3,100 m) and Peru (4,300 m) birth weights averaged 3,186±70 g and 2,920±90 g respectively. A sample of 15 births from Tibet (3,658 m) weighed 3,307±110 g which was more than their altitude counterparts and close to sea-level norms. Pregnancy increased maternal ventilation at all three study sites. In Peru, the resultant elevation in arterial O₂ saturation offset the pregnancy-induced fall in hemoglobin concentration to preserve arterial O₂ content at nonpregnant levels. Arterial O₂ content decreased slightly in Colorado and more markedly in Tibet in the pregnant compared to the nonpregnant state. The Colorado and Peru women with the greatest rise in ventilation and ventilatory sensitivity to hypoxia produced the heaviest birthweight infants, suggesting that maternal arterial oxygenation was an important determinant of fetal growth. The pregnant women in Tibet did not have higher levels of arterial O₂ content than the pregnant Colorado or Peru women nor did maternal arterial O₂ content relate to birth weight in Tibet. Infant birth weight in Tibet tended to be correlated with the ratio of uterine artery to common iliac artery mean flow velocity, suggesting that redistribution of lower-extremity blood flow to favor the uterine circulation may have acted to augment uterine O₂ delivery in the Tibet women. Thus, the limited data available suggested that the Tibetans may be better adapted as judged by less fetal growth retardation and may utilize maternal O₂ transport mechanisms not reliant upon increased arterial O₂ content.     

Pancreatic O2 consumption and CO2 output during secretin-induced,exocrine secretion from the pancreas in the anesthetized dog

Secretin stimulates pancreatic water and CO₂ excretion as well as pancreatic blood flow. It has been questioned whether the production (i.e. water and CO₂ excretion) is reflected in the input-output difference of nutrients. In pentobarbital anesthetised dogs, pancreatic exocrine secretion was stimulated by secretin, (Karolinska), 1 U/kg injected as an i.v. bolus. Secretion was maximally increased at 2 min after the secretin shot and returned to a basal value at between 16 and 32 min after secretin. Blood flow was also maximally increased at 2 min, but decreased to the basal value at between 8 and 16 min. O₂ extraction first decreased (at 2 min) and then gradually increased until it was higher than the basal value (at 16 min) and then returned to the basal level (at 32 min). O₂ consumption increased quickly, reached a plateau, lasting from 1 to 16 min, and then decreased to the basal level (32 min). CO₂ transfer from blood to tissue reached a maximum at 4 min and then decreased to the basal value (at between 16 and 32 min). The curves for CO₂ transfer from tissue to pancreatic secretion and for CO₂ in the secretion had the same shape. It is concluded that the curve of production (of water and CO₂ excretion) parallels the curve of O₂ consumption fairly well. The O₂ consumption curve did not correlate either with the blood flow curve or with the O₂ extraction curve. About one quarter of the excreted CO₂ originated from pancreatic metabolism and the remaining three quarters were transferred from blood, through the pancreatic tissue into the secretion. The increase in O₂ consumption was achieved by an increase in blood flow, followed by an increase in O₂ extraction. The release of a vasodilator metabolite by the pancreatic cells upon arrival of the secretin molecules, may explain both the increase in blood flow and the successive increase in O₂ extraction. Therefore these data can be interpreted according to the model for metabolic control of tissue oxygenation.     

Hypophagia-induced hypometabolism during experimental anaemia in rats

Several investigators have reported a drop in oxygen (O₂) consumption (VO₂) and body temperature in laboratory animals during normobaric or hypobaric hypoxia. Hypophagia, with normal efficiency of protein utilisation for growth, was also observed. It has recently also been observed that hypometabolism is present during anaemic hypoxia. The present study was designed to test the experimental hypothesis that anaemic hypoxia induces hypometabolism secondary to hypophagia. Episodes of anaemia were created in adult male rats by either blood withdrawal through cardiac puncture (haemorrhagic anaemia) or phenylhydrazine administration (haemolytic anaemia). Haematrocrit, VO₂, and food consumption, as indirect estimations of the level of anaemia, energy production, and appetite, respectively, were serially measured in all animals during 7 days (acute experiments) or 17 days (chronic experiments). Positive correlations were found between the three parameters during development of and recovery from anaemia during each anaemic episode. When the amount of food offered to non-anaemic rats was equalised to that freely eaten by anaemic rats, VO₂ dropped in the former to almost the level found in the latter. Body composition changed during chronic anaemia because of a decrease in the lipid fraction of the body. The results confirmed the working hypothesis that hypometabolism, which has been considered as an immediate, emergency-type response to both hypoxic and anaemic hypoxia, can be considered as a response secondary to hypophagia because of depressed appetite. How appetite is adapted to the mechanisms which control O₂ convection and O₂ availability is not known at present.     

Modelling study of the acute cardiovascular response to hypocapnic hypoxia in healthy and anaemic subjects

The present study analyses the cardiovascular response to acute hypocapnic hypoxia (simulating the effect of respiration at high altitude) both in healthy, unacclimatised subjects and in subjects with moderate anaemia, by means of a mathematical model of short-term cardiovascular regulation. During severe hypoxia, cardiac output and heart rate (HR) exhibit a significant increase compared with the basal level (cardiac output: +90%; HR: +64%). Systemic arterial pressure remains quite constant or shows a mild increase. Coronary blood flow increases dramatically (+200%), thus maintaining a constant oxygen delivery to the heart. However, blood oxygen utilisation in the heart augments, to fulfil the increased power of the cardiac pump during hypoxia. Cerebral blood flow rises only at very severe hypoxia but, owing to the vasoconstrictory effect of hypocapnia, its increase (+80%) is insufficient to maintain oxygen delivery to the brain. The model suggests that a critical level for the aerobic metabolism in these organs (heart and brain) is reached at an oxygen partial pressure in arterial blood (PaO₂) of approximately 25 mmHg. Moderate anaemia during normoxia is compensated by an increase in cardiac output (+22%), a decrease in total peripheral resistance (−30%) and an increase in O₂ extraction from blood (+40%). As cardiovascular regulation mechanisms are already recruited in anaemic subjects at rest, their action soon becomes exhausted during hypocapnic hypoxia. Critical levels for vital functions are already reached at a PaO₂ of approximately 45 mmHg.     

Coronary blood flow in rats native to simulated high altitude and in rats exposed to it later in life

Summary In rats exposed to a simulated high altitude of 3500 m for their whole prenatal and postnatal life a severe cardiac hypertrophy develops. In rats born and first staying 5 weeks at sea level and then being exposed to simulated high altitude, only a unilateral right cardiac hypertrophy occurs. In both groups nutritional coronary blood flow was estimated in left ventricle, right ventricle, and septum and was compared with control animals of similar age. Coronary blood flow was measured at hypoxia in all groups. At first cardiac output was determined by the Fick principle, then⁸⁶Rb was applied and the animals were killed after 55 sec. Activity of⁸⁶Rb was measured in both cardiac ventricles and septum and the fractional uptake was calculated. According to Sapirstein (1956, 1958) the distribution of⁸⁶Rb follows the distribution of cardiac output and from both these data the nutritional blood flow to the parts of the heart may be estimated.Cardiac output was similar in rats exposed to simulated high altitude later in life (newcomers) and in control animals, but it was significantly lower in rats born in the low pressure chamber (natives).Fractions of cardiac output supplying cardiac ventricles and septum in rats from both hypoxic groups were significantly higher than in control animals. In the natives they were significantly higher than in the newcomers. The fractions of cardiac output in both newcomers and natives remained significantly higher than those of the control animals, also when calculated per gram of heart tissue.Nutritional coronary blood flow (in ml/min) was higher in both ventricles and septum of the newcomers and in the right ventricle of the natives, and lower in the septum of the natives, when compared with control animals. Coronary blood flow per gram of heart tissue (in ml/min·g) was significantly higher in all cardiac parts of the newcomers, but it was about the same in all cardiac parts of the natives when compared with controls.The importance of observed changes concerning myocardial tissue oxygenation is analyzed by using Krogh's cylindrical tissue model.Presented in part at the XXVIth International Congress of Physiological Sciences, New Delhi, India, October 20–26, 1974.     

Effects of severe arterial hypocapnia on regional blood flow regulation,tissuePO2 and metabolism in the brain cortex of cats

The effect of a stepwise decrease inPaCO₂ from 3.9–1.6 kPa on rCBF, rCMRO₂, tissuePO₂ and concentrations of glucose, lactate, pyruvate, ATP, ADP, AMP and phosphocreatine in the brain cortex was studied in cats lightly anaesthetized with sodium pentobarbital. 1. Moderate lowering ofPaCO₂ to 2.5 kPa induced in all animals a homogeneous decrease of rCBF in corresponding areas of the right and left hemisphere. Mean rCBF fell from 129.2 to 103.1 ml · 100 g^–1 · min^–1, while rCMRO₂ remained unchanged (12.7–12.9 ml · 100 g^–1 · min^–1). The tissuePO₂ frequency histograms showed a shift to lower values without indicating the presence of brain tissue hypoxia. 2. Severe arterial hypocapnia (PaCO₂=1.6 kPa) caused an inhomogeneous blood flow reaction. Both further decreased as well as increased rCBF values were measured simultaneously in the brain cortex of individual animals (mean rCBF=97.6 ml · 100 g^–1 · min^–1). At the same time tissuePO₂ measurements and metabolite assays indicated the presence of pronounced brain tissue hypoxia. The tissue concentrations of lactate and pyruvate and the lactate/pyruvate ratio were significantly increased, while the phosphocreatine concentration was significantly reduced. In addition, rCMRO₂ decreased to 11.3 ml · 100 g^–1 · min^–1. The results provide conclusive evidence that severe arterial hypocapnia leads to an insufficient O₂ supply of the brain cortex, which in turn seems to counteract the influence of hypocapnia on cortical blood flow regulation.Preliminary reports of these investigations were presented at the International Symposium on Oxygen Transport to Tissue, July 9–11, 1980 in Budapest and at the Second International Symposium on Pathophysiology and Pharmacotherapy of Cerebrovascular Disorders, July 22–25, 1980 in Tübingen, FRG     

Effects of breathing control on cardiocirculatory modulation in Caucasian lowlanders and Himalayan Sherpas

This study was performed to investigate the influence of breathing control on the autonomic cardiac regulation at high altitude in adapted and non-adapted awake subjects. We recorded electrocardiogram and pulse oximetry in 14 short-term acclimatized lowlanders and 14 Himalayan Sherpas during resting conditions at an altitude of 5,050 m. Spectrum analysis was performed on synchronized 15 min periods of R-R intervals and the oxygen saturation of arterial blood (S_aO₂). Despite mean S_aO₂ being similar in lowlanders and Himalayan Sherpas [78.5 (SD 7.0)% compared to 79.4 (SD5.8)%, respectively], fluctuations in S_aO₂ were significantly increased in lowlanders compared to Sherpas, thus indicating an unstable regulation of respiration control in lowlanders. Regression analysis demonstrated a significant relationship between spectrum power of S_aO₂ and the relative power of R-R intervals in the frequency band between 0.01 and 0.08 Hz in lowlanders, but not in Sherpas. Our results demonstrate differences in respiratory and autonomic cardiac control between non-adapted lowlanders and Himalayan high-altitude residents and indicate that unstable breathing control during chronic hypobaric hypoxia is significantly correlated with the autonomic cardiocirculatory regulation. Accepted: 11 September 2000     

Exercise induced augmentation of myocardial oxygen extraction in spite of normal coronary dilatory capacity in dogs

Summary Myocardial O₂-extraction rate was studied during exercise induced augmentation of cardiac work in dogs.The O₂-extraction rate at rest was 75% of arterial content. Progressive levels of exercise increased the animals' O₂-consumption from 7 ml/min · kg up to 91 ml/min · kg. Cardiac output rose from 108 ml/min · kg at rest to 484 ml/min · kg at the highest exercise level. The increase in myocardial O₂-consumption from 9 ml/min·100 g at rest up to 57 ml/min·100 g at the highest exercise level was met by an increase in coronary flow from 59 to 256 ml/min·100 g and a rise of myocardial AVDO₂ from 15 to 22 Vol%. Thus the latter contributed 40% to the augmented myocardial O₂-requirements.Coronary venous O₂-saturation decreased to 9% saturation during highest levels of exercise. This low value was not the result of a limited coronary dilatory capacity, of inadequate state of exercise training, or of a relative underperfusion of the inner layers of the left ventricle.Thus, augmentation of myocardial O₂-extraction rate seems to be a mechanism of physiological relevance during exercise induced elevation of myocardial O₂-requirements in dogs and may be explained by capillary recruitment in the myocardium.Supported by Deutsche Forschungsgemeinschaft     

Venous but not skeletal muscle interstitial nitric oxide is increased during hypobaric hypoxia

Systemic hypoxia leads to peripheral vasodilation that serves to counteract the decrease in peripheral oxygen (O₂) delivery. Skeletal muscle vasodilation associated with hypoxia is due to release of vasodilator substances such as adenosine and/or nitric oxide (NO). We hypothesized that skeletal muscle may act as a source of NO during exposure to hypoxia. Therefore, we measured NO in forearm venous plasma and in skeletal muscle interstitial dialysate in seven healthy young men during exposure to simulated altitude of 2,438 and 4,877 m (20 min at each level) in a hypobaric chamber. O₂ saturation (mean ± SEM) fell from 98.0 ± 0.2% at ambient conditions to 91.0 ± 0.4% at 2,438 m and to 73.2 ± 4.4% at 4,877 m (P < 0.05). While blood pressure remained unchanged, heart rate increased in a graded fashion (P < 0.05). Plasma NO (chemiluminescence method) rose from 11.6 ± 1.3 to 16.9 ± 2.9 μM at 2,438 m (P < 0.05) but remained similar at 16.4 ± 2.3 μM at 4,877 m (NS). In contrast, skeletal muscle microdialysate NO levels were lower than plasma NO (P < 0.01) and did not change during simulated altitude. Thus, hypoxia produced by simulated high altitude exposure leads to an increase in plasma but not skeletal muscle interstitial NO. These data support an important role of NO in the peripheral vascular responses to hypoxia. The differential responses of plasma vs. interstitial NO during hypoxia suggest an endothelial or intravascular source of NO.     

Acid-base balance and O2 transport at high altitude

Ear lobe blood pH_a, P_aCO ₂, P_aO ₂, and O₂ saturation (S_aO₂) were measured in healthy Caucasians and Sherpas at 3400 m (Namche Bazaar, Nepal, n=4/5), 5050 m (Pyramid Laboratory, Lobuche, Nepal, n=20/5) and 6450 m (Camp II of Mt Everest, n=11/7). In the investigated altitude range, pH_a increased progressively with altitude from 7.463±0.005 (mean±SE) to 7.496±0.006 in Caucasians whereas it remained essentially constant (7.45–7.46) in Sherpas. At all altitudes, P_aCO ₂ was higher in Sherpas than in Caucasians (P<0.02). By contrast, P_aO ₂ and S_aO₂ were the same in Caucasians and Sherpas at all investigated altitudes. Moreover, in Caucasians sojourning for 3 weeks at 5050 m, P_aCO ₂ kept decreasing whereas pH_a, P_aO ₂ and S_aO₂ remained constant. These data suggest that: (1) respiratory alkalosis was a common finding both in Caucasians and Sherpas; (2) at 6450 m, Sherpas were less alkalotic due to higher P_aCO ₂ than Caucasians, possibly a consequence of a blunted ventilatory response; (3) at 6450 m, S_aO₂ and P_aO ₂ were the same in Caucasians and Sherpas despite different P_aCO ₂ values. The latter finding could be the consequence of one or more of the following adjustments in Sherpas: (1), an increased efficiency of alveolar O₂ transfer, i.e. smaller alveolar-arterial O₂ gradient; (2) a decreased (arterial – mixed venous) O₂ difference, possibly due to increased cardiac output; (3) a reduced increase of the [2,3-DPG]/[Hb] ratio; but not (4) an elevated gas exchange ratio (R). It is concluded that both physiological and biochemical variables contribute to optimize the O₂ transport at altitude. Apparently a more efficient adaptation to hypoxia allows Sherpas to limit alkalosis through a lower ventilatory drive and to maintain S_aO₂ at the same P_aO ₂ by decreasing the [2,3-DPG]/[Hb] ratio.     

Changes in performance,maximal oxygen uptake and maximal accumulated oxygen deficit after 5, 10 and 15 days of live high:train low altitude exposure

Nineteen well-trained cyclists (14 males and 5 females, mean initial V˙O_2max 62.3 ml kg^–1 min^–1) completed a multistage cycle ergometer test to determine maximal mean power output in 4 min (MMPO_4min), maximal oxygen uptake (V˙O_2max) and maximal accumulated oxygen deficit (MAOD). The athletes were divided into three groups, each of which completed 5, 10 or 15 days of both a control condition (C) and live high:train low altitude exposure (LHTL). The C groups lived and trained at the ambient altitude of 610 m. The LHTL groups spent 8–10 h night^–1 in normobaric hypoxia at a simulated altitude of 2,650 m, and trained at the ambient altitude of 610 m. The changes to MMPO_4min, V˙O_2max and MAOD in response to LHTL altitude exposure were not significantly different for the 5-, 10- and 15-day treatment periods. For the pooled data from all three treatment periods, there were significant increases in MMPO_4min [mean (SD) 5.15 (0.83) W kg^–1 vs 5.34 (0.78) W kg^–1] and MAOD [50.1 (14.2) ml kg^–1 vs 54.9 (13.1) ml kg^–1] in the LHTL athletes between pre- and post-altitude exposure. There were no significant changes in MMPO_4min [5.09 (0.76) W kg^–1 vs 5.16 (0.86) W kg^–1] or MAOD [50.5 (14.1) ml kg^–1 vs 49.1 (13.0) ml kg^–1] in the C athletes over the corresponding period. There were significant increases in V˙O_2max in the athletes during both the LHTL [63.2 (9.0) ml kg^–1 min^–1 vs 64.1 (9.0) ml kg^–1 min^–1] and C [62.0 (8.6) ml kg^–1 min^–1 vs 63.4 (9.2) ml kg^–1 min^–1] conditions. In these athletes, there was no difference in the impact of 5, 10 or 15 days of LHTL on the increases observed in MMPO_4min, V˙O_2max or MAOD; and LHTL increased MMPO_4min and MAOD more than training at low altitude alone. Electronic Publication     

Transcutaneous,noninvasiveP O 2 monitoring in adults during exercise and hypoxemia

A new, commercially available, transcutaneous (tc)P _{O 2} monitor was tested in adult females and in laboratory animals to assess its applicability in measuring arterial oxygen tension during physiological stress. Observed values on dogs correlated well with direct measurements of arterialP _{O 2} and with previous data obtained from measurements of arterial blood during exercise and hypoxemia. In our female subjects the unit responded rapidly to changes in inspired ambient oxygen and electrical stability was excellent during maximal exercise tests. TranscutaneousP _{O 2} decreased to an average of 87.8 Torr during maximum exercise breathing 20.9% O₂, and to 32 Torr while breathing 12.6% O₂ at maximum work. Two distinct patterns of response in tcP _{O 2} were observed during hypoxic and normoxic exercise. The technique appears to have substantial future application both in clinical and physiological investigation involving adult subjects.