Effects of high altitude exposure on components of blood and urine in mountaineers

Physiological correlations with impaired or umimpaired performance at high altitude were sought among 24 blood and urine parameters measured in 50 mountaineers and 21 observers before (preclimb) and after (postclimb) expeditions on Mt. McKinley. Values and per cent changes were compared for five degrees of impairment at high altitude. Average preclimb values were all near established normal levels and no correlations with subsequent involvement at high altitude were found. Postclimb samples contained more Hb, PCV, urea, LDH, and HBD and less bilirubin (P < 0.05). But no association was found between degrees of altitude impairment and preclimb/postclimb changes in any of the 24 blood and urine parameters. Additional results from samples collected at 4300 m showed "weaker" mountaineers excreted 1/4 as much Na in urine and had 50% more serum FFA concentration than stronger mountaineers.

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Zusammenfassung Bei 50 Bergsteigern und 21 Beobachtern wurden vor und nach einer Expedition zum Mt. McKinley (Alaska) für 24 Parameter im Blut und Harn die Beziehungen zur Abschwächung der Leistung in grosser Höhe untersucht. Zum Vergleich wurden 5 Grade von unbeeinflusster bis schwerer Schädigung in der Höhe verwendet. Die mittleren Werte vor dem Aufstieg lagen alle im Bereich der Normbreite. Beziehungen zu nachfolgenden Komplikationen in der Höhe bestanden nicht. Nach dem Aufstieg waren Hgb, Hämatokrit, Harnstoff, LDH, Hydroxybutyric Dehydrogenase erhöht und Bilirubin erniedrigt (P < 0, 05). Es liess sich jedoch für keinen Parameter eine Beziehung zwischen dem Ausmass der Höhenschädigung und den Veränderungen vor und nach dem Aufstieg nachweisen. Zusätzliche Ergebnisse von Proben, die in 4300 m Höhe gesammelt wurden, ergaben, dass schwache Bergsteiger ein Viertel soviel Na im Harn ausschieden und 50% mehr freie Fettsäuren im Blut aufwiesen als starke Bergsteiger.

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Resume On a mesuré 24 paramètre du sang et de l'urine de 50 alpinistes et 21 observateurs avant et après l'ascension du Mont McKinley (Canada). On a établi ensuite la corrélation physiologique existant entre ces paramètres et une diminution éventuelle des performances. Les valeurs absolues et le taux de modification ont été comparés à 5 degrés de diminution des capacités physiques à haute altitude. Les valeurs moyennes des analyses faites avant l'ascension ont toutes été voisines du niveau normal et on n'a pas constaté de corrélation avec les performances individuelles subséquentes. Les échantillons recueillis après l'ascension contenaient davantage de Hb, PCV, urée, LDH, et HBD, mais moins de bilirubine (P < 0, 05). On n'a cependant trouvé aucune relation entre le degré de diminution des performances et les modifications d'aucun des 24 paramètres retenus du sang ou de l'urine avant et après l'ascension. Des échantillons prélevés à 4300 m d'altitude ont montré que les alpinistes peu aguerris ne sécrétaient que le 1/4 du Na par l'urine, mais avaient 50% d'acides gras libres de plus dans le sang que les montagnards les plus résistants.

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Work supported by Themis Contract No DADA 17-68-C-8018     

Changes in fibrinolysis components during short-term adaptation to high altitude]

In studying hemocoagulation in dogs under conditions of Frunze (760 m above the sea level) and Tuya-Ashu (3200 m above the sea level) it was shown that in the "emergency" phase of adaptation (the first three days) there was seen activation of fibrinolysin and profibrinolysin with depression of antifibrinolysins and inhibitors of profibrinolysin activators. The concentration of plasma fibrinogen at that period decreased by 100 mg%, which could promote an increase in the vascular permeability and improvement of oxygen approach to the tissues. Later, along with elevation of fibrinolysin and profibrinolysin activators there was a marked increase in the level of fibrinolysis inhibitors. Correlation of all the fibrinolysis components was established at a new level.     

Thoracic adaptation to high altitude

Growth in the thoracic region and its adaptation to higher altitude was investigated in boys between 5 to 18 years of Rajput origin at two altitudes, i. e. Rampur Bushahr (800 m above sea level) and Kinnaur (3,000 m above sea level). Both places are located in Himachal Pradesh. The sample includes 405 individuals From Bushahr and 676 individuals from Kinnaur. The results of this study reveal that as the higher altitudes are attained the vital capacity also increases relatively more, and these differences become more pronounced after adolescence, indicating longer time of apnoea. The population living at higher altitudes is also characterised by a significant greater chest length.     

Sleep of Andean high altitude natives.

The structure of sleep in lowland visitors to altitudes greater than 4000 m is grossly disturbed. There are no data on sleep in long-term residents of high altitudes. This paper describes an electroencephalographic study of sleep in high altitude dwellers who were born in and are permanent residents of Cerro de Pasco in the Peruvian Andes, situated at 4330 m. Eight healthy male volunteers aged between 18 and 69 years were studied. Sleep was measured on three consecutive nights for each subject. Electroencephalographs, submental electromyographs and electro-oculograms were recorded. Only data from the third night were used in the analysis. The sleep patterns of these subjects resembled the normal sleep patterns described by others in lowlanders at sea level. There were significant amounts of slow wave sleep in the younger subjects and rapid eye movement sleep seemed unimpaired.     

动物对高原低氧的适应性研究进展

本文从血液学、肺动脉、心肺发育及其它方面简要介绍了动物对高原低氧适应的生理、生化及形态学特征,同时也对其中低氧诱导因子的作用及其遗传性方面的研究进行了概述。关于高原低氧适应的遗传机制仍需进一步的深入研究。     

Developmental adaptation to high altitude hypoxia

Experimental studies on animals and humans exposed to hypoxic stress have been reviewed. These data suggest that the influence of hypoxic stress, and the organism's response to it, are greater during growth than during adulthood. The organism's responses include alterations in the quantity and size of the alveolar units of the lungs, enlargement of the right ventricle of the heart, slower somatic growth as measured by birth weight and body size, increased aerobic capacity during maximal work, and greater control of ventilation. It is postulated that the organism is more sensitive to the influence of environmental factors during growth and development than during adulthood. Consequently, adaptive traits acquired during the developmental period have profound, long-term consequences, which are reflected in the physiological and morphological characteristics of the adult organism. It is concluded that the differences between the highland and lowland natives in their physiological performance and morphology are mostly due to adaptations acquired during the developmental period.Attention is called to the fact that the principle of developmental sensitivity and plasticity does not imply equally adaptive responses in all biological parameters. In other words, what we consider a deficiency in a given variable may actually reflect the indirect influence of the adaptive success of another variable.Presented at the Seventh International Biometeorological Congress, 17–23 August 1975, College Park Maryland, USA.     

Aspects of physical activity in high altitude natives

Altitude adaptation was measured at sea level and high altitudes in sea level adapted and high altitude adapted natives. Tests of work capacity as measured by O₂ consumption, pulse rate, and ventilation rate are reported. It is noted that comparing our results with those of other investigators is difficult due to variations in terminology and procedure. This suggests the necessity of more precise definitions in studies of the physical activity of high altitude natives.     

Carbonic anhydrase activity in the red blood cells of sea level and high altitude natives

Red blood cell carbonic anhydrase (CA) activity has not been studied in high altitude natives. Because CA is an intraerythocytic enzyme and high altitude natives are polycythemic, it is important to know if the activity of CA per red cell volume is different from that of their sea level counterparts. Blood was collected from healthy subjects living in Lima (150m) and from twelve subjects from Cerro de Pasco (4330m), and hematocrit and carbonic anhydrase activity were measured. As expected, the high altitude natives had significantly higher hematocrits than the sea level controls (p = 0.0002). No difference in the CA activity per milliliter of red cells was found between the two populations. There was no correlation between the hematocrit and CA activity.     

Pulmonary capillary blood volume and membrane conductance in Andeans and lowlanders at high altitude: A cross-sectional study

Lung carbon monoxide (CO) transfer and pulmonary capillary blood volume (Vc) at high altitudes have been reported as being higher in native highlanders compared to acclimatised lowlanders but large discrepancies appears between the studies. This finding raises the question of whether hypoxia induces pulmonary angiogenesis.Eighteen highlanders living in Bolivia and 16 European lowlander volunteers were studied. The latter were studied both at sea level and after acclimatisation to high altitude. Membrane conductance (Dm_CO) and Vc, corrected for the haemoglobin concentration (Vc_cor), were calculated using the NO/CO transfer technique. Pulmonary arterial pressure and left atrial pressures were estimated using echocardiography.Highlanders exhibited significantly higher NO and CO transfer than acclimatised lowlanders, with Vc_cor/VA and Dm_CO/VA being 49 and 17% greater (VA: alveolar volume) in highlanders, respectively. In acclimatised lowlanders, Dm_CO and Dm_CO/VA values were lower at high altitudes than at sea level. Echocardiographic estimates of cardiac output and pulmonary arterial pressure were significantly elevated at high altitudes as compared to sea level.The decrease in Dm_CO in lowlanders might be due to altered gas transport in the airways due to the low density of air at high altitudes. The disproportionate increase in Vc in Andeans compared to the change in Dm_CO suggests that the recruitment of capillaries is associated with a thickening of the blood capillary sheet. Since there was no correlation between the increase in Vc and the slight alterations in haemodynamics, this data suggests that chronic hypoxia might stimulate pulmonary angiogenesis in Andeans who live at high altitudes.     

Selected contribution: High-altitude natives living at sea level acclimatize to high altitude like sea-level natives.

Sea-level (SL) natives acclimatizing to high altitude (HA) increase their acute ventilatory response to hypoxia (AHVR), but HA natives have values for AHVR below those for SL natives at SL (blunting). HA natives who live at SL retain some blunting of AHVR and have more marked blunting to sustained (20-min) hypoxia. This study addressed the question of what happens when HA natives resident at SL return to HA: do they acclimatize like SL natives or revert to the characteristics of HA natives? Fifteen HA natives resident at SL were studied, together with 15 SL natives as controls. Air-breathing end-tidal Pco(2) and AHVR were determined at SL. Subjects were then transported to 4,300 m, where these measurements were repeated on each of the following 5 days. There were no significant differences in the magnitude or time course of the changes in end-tidal Pco(2) and AHVR between the two groups. We conclude that HA natives normally resident at SL undergo ventilatory acclimatization to HA in the same manner as SL natives.     

Hemoglobin levels in high altitude Tibetan natives of northwest Nepal

Unusually low hemoglobin levels were found in a healthy population of Tibetan speaking people residing at 3800 m along the Nepal-Tibet frontier in northwest Nepal. Peoples native to the Tibetan plateau may have evolved novel adaptive strategies to hypoxic stress.     

Ventilation and hypoxic ventilatory response of Tibetan and Aymara high altitude natives

Newcomers acclimatizing to high altitude and adult male Tibetan high altitude natives have increased ventilation relative to sea level natives at sea level. However, Andean and Rocky Mountain high altitude natives have an intermediate level of ventilation lower than that of newcomers and Tibetan high altitude natives although generally higher than that of sea level natives at sea level. Because the reason for the relative hypoventilation of some high altitude native populations was unknown, a study was designed to describe ventilation from adolescence through old age in samples of Tibetan and Andean high altitude natives and to estimate the relative genetic and environmental influences. This paper compares resting ventilation and hypoxic ventilatory response (HVR) of 320 Tibetans 9–82 years of age and 542 Bolivian Aymara 13–94 years of age, native residents at 3,800–4,065 m. Tibetan resting ventilation was roughly 1.5 times higher and Tibetan HVR was roughly double that of Aymara. Greater duration of hypoxia (older age) was not an important source of variation in resting ventilation or HVR in either sample. That is, contrary to previous studies, neither sample acquired hypoventilation in the age ranges under study. Within populations, greater severity of hypoxia (lower percent of oxygen saturation of arterial hemoglobin) was associated with slightly higher resting ventilation among Tibetans and lower resting ventilation and HVR among Aymara women, although the associations accounted for just 2–7% of the variation. Between populations, the Tibetan sample was more hypoxic and had higher resting ventilation and HVR. Other systematic environmental contrasts did not appear to elevate Tibetan or depress Aymara ventilation. There was more intrapopulation genetic variation in these traits in the Tibetan than the Aymara sample. Thirty-five percent of the Tibetan, but none of the Aymara, resting ventilation variance was due to genetic differences among individuals. Thirty-one percent of the Tibetan HVR, but just 21% of the Aymara, HVR variance was due to genetic differences among individuals. Thus there is greater potential for evolutionary change in these traits in the Tibetans. Presently, there are two different ventilation phenotypes among high altitude natives as compared with sea level populations at sea level: lifelong sustained high resting ventilation and a moderate HVR among Tibetans in contrast with a slightly elevated resting ventilation and a low HVR among Aymara. Am J Phys Anthropol 104:427–447, 1997. © 1997 Wiley-Liss, Inc.     

Genetic adaptation to high altitude in the Ethiopian highlands

Background

Genomic analysis of high-altitude populations residing in the Andes and Tibet has revealed several candidate loci for involvement in high-altitude adaptation, a subset of which have also been shown to be associated with hemoglobin levels, including EPAS1, EGLN1, and PPARA, which play a role in the HIF-1 pathway. Here, we have extended this work to high- and low-altitude populations living in Ethiopia, for which we have measured hemoglobin levels. We genotyped the Illumina 1M SNP array and employed several genome-wide scans for selection and targeted association with hemoglobin levels to identify genes that play a role in adaptation to high altitude.

Results

We have identified a set of candidate genes for positive selection in our high-altitude population sample, demonstrated significantly different hemoglobin levels between high- and low-altitude Ethiopians and have identified a subset of candidate genes for selection, several of which also show suggestive associations with hemoglobin levels.

Conclusions

We highlight several candidate genes for involvement in high-altitude adaptation in Ethiopia, including CBARA1, VAV3, ARNT2 and THRB. Although most of these genes have not been identified in previous studies of high-altitude Tibetan or Andean population samples, two of these genes (THRB and ARNT2) play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. These combined results suggest that adaptation to high altitude arose independently due to convergent evolution in high-altitude Amhara populations in Ethiopia.     

Control of breathing and adaptation to high altitude in the bar-headed goose

The bar-headed goose flies over the Himalayan mountains on its migratory route between South and Central Asia, reaching altitudes of up to 9,000 m. We compared control of breathing in this species with that of low-altitude waterfowl by exposing birds to step decreases in inspired O(2) under both poikilocapnic and isocapnic conditions. Bar-headed geese breathed substantially more than both greylag geese and pekin ducks during severe environmental (poikilocapnic) hypoxia (5% inspired O(2)). This was entirely due to an enhanced tidal volume response to hypoxia, which would have further improved parabronchial (effective) ventilation. Consequently, O(2) loading into the blood and arterial Po(2) were substantially improved. Because air convection requirements were similar between species at 5% inspired O(2), it was the enhanced tidal volume response (not total ventilation per se) that improved O(2) loading in bar-headed geese. Other observations suggest that bar-headed geese depress metabolism less than low-altitude birds during hypoxia and also may be capable of generating higher inspiratory airflows. There were no differences between species in ventilatory sensitivities to isocapnic hypoxia, the hypoxia-induced changes in blood CO(2) tensions or pH, or hypercapnic ventilatory sensitivities. Overall, our results suggest that evolutionary changes in the respiratory control system of bar-headed geese enhance O(2) loading into the blood and may contribute to this species' exceptional ability to fly high.