Hemoglobin levels in a Himalayan high altitude population

This report presents data on hemoglobin concentrations in a sample of Himalayan high altitude natives measured at their habitual altitude of residence. In this sample of 270 healthy Tibetan adults resident at 3250–3560 m in Upper Chumik, Nepal, the mean hemoglobin concentration is 16.1 ± 1.2 gm/dl among adult males, 14.4 ± 1.4 gm/dl among premenopausal and 15.0 ± 1.1 gm/dl among postmenopausal adult females. 123 of 126 (98%) males, 96 of 100 (96%) premenopausal and 36 of 44 (82%) postmenopausal females have hemoglobin concentrations within two standard deviations of the sea level mean. These data demonstrate that a healthy population may reside at high altitude without the degree of elevation in hemoglobin widely known and cited for Andean highlanders. Comparing published data on mean hemoglobin concentrations of adult Himalayan and Andean samples residing between 3200 m and 4100 m reveals that Himalayan means are systematically lower. This in turn may account for the reported population differences in the prevalence of chronic mountain sickness (Monge's disease). It is hypothesized that Himalayan and Andean highlanders represent alternative patterns of high altitude hematological adaptation.     

Secular change in growth of native children and adolescents at high altitude I. Puno,Peru (3800 meters)

A cross sectional sample of 969 native males from Puno (Peru), altitude 3800 m, ranging in age from 7–20 years, and studied for body height, weight, sitting height, leg length, and chest circumference in 1980, were compared, from the point of view of secular trend, with another cross sectional sample of 992 native males from the same place, which were investigated in 1945. In addition, similar observations were carried out in 1980, in a group of 112 females. The data indicate that in Puno there has been no secular increment in the adult body size. However for all ages between 7 and 19 years, body weight and height were significantly greater in 1980 than in 1945. This may be due to earlier sexual maturation in the present generation.     

Effect of yogic exercises on thyroid function in subjects resident at sea level upon exposure to high altitude

Using radioactive iodine, the effect of 1 month's yogic exercises has been investigated on the thyroid function of subjects resident at sea level (SL) specially after their exposure to high altitude (HA). The results have been compared with a group of SL subjects who underwent physical training (PT) exercises for the same duration. Ten healthy male volunteers in the age range of 20–30 years were used as test subjects in this study with each serving as his own control. The subjects were randomly divided into two groups of 5 each. One group practised hatha yogic exercises, while the other group performed the regular PT exercises. The thyroidal accumulation and release of radioactive iodine have been measured in each of the subjects of both groups before and after 1 month of their respective exercises at SL. One month of yogic exercises at SL has been observed to cause a significant reduction in the trans-thy-roidal availability of radioiodine. The thyroid radioactivity in this group of subjects was always below normal levels with the exception of two peaks of radioactive iodine uptake, when the levels of radioactivity in the thyroid were similar to the control values of pre-yogic exercises. The release of radiolabel at 24–48 h was significantly increased after yogic exercises. In contrast, the subjects performing PT exercises for the same duration at SL showed significant thyroid uptake of radioactive iodine at 24 h. Subsequently their¹³¹I uptake continued to rise slowly until 72 h without any demonstrable thyroidal release of radiolabel. This indicated that increased thyroid activity was induced by conventional PT exercise. Exposure of SL residents to HA irrespective of their exercise regime altered the thyroidal handling of radioiodine. Thyroidal concentrations of freshly administered radioiodine at early and late sampling intervals were very high in both of the groups, especially the yogics, after their return to SL from HA. Possible mechanisms of the observed changes have been discussed.     

Growth of lowland native children of European Ancestry during sojourn at high altitude (3,200 m)

The moderate growth retardation frequently observed among children living at high altitude is usually assumed to result from hypoxic stress. However, such children are frequently from the poorer socioeconomic strata of their societies and may suffer malnutrition, poor hygiene, inadequate medical care, and overcrowding—factors also associated with growth retardation. The objective of this study was to determine if there is a statistically observable alteration in the growth of middle-class children of European ancestry during sojourn at high altitude. Semilongitudinal height/weight measurements were gathered retrospectively from medical records of 18 boys and 17 girls who were born at low altitude, were well-nourished and clinically normal, and who had lived at Achoma, Peru (altitude 3,200 m), continuously for 9–36 months. Measurements were divided, by sex, into four cohorts: I (3–6 months at Achoma), II (6–12 months), III (12–18 months), and IV (18–24 months); initial, presojourn, height and weight were also obtained. All heights and weights were normalized with age-specific reference values. Changes in Z scores (ΔZ) during sojourn were calculated for each subject by subtracting the score of the presojourn value from those of cohorts I–IV. Paired t-tests revealed, among the boys, a significant decline in Z score for weight during sojourn in all four cohorts. Weight scores for the girls also declined in all four cohorts, although only the change in cohort III was significant. Height scores showed a decline with time at sojourn in the boys, but in girls there is an initial drop followed by a steady increase to presojourn levels. These results are consistent with the view that moderate hypoxia exerts a primary growth-limiting effect even on healthy, well-nourished children.     

Human nutrition in cold and high terrestrial altitudes

The calorie and nutritional requirements for a man working in an alien hostile environment of cold regions and high altitude are described and compared to those of normal requirements. Carbohydrates, fats and vitamins fulfilling the caloric and nutritional requirements are generally available in adequate amounts except under conditions of appetite loss. However, the proteins and amino acids should be provided in such a way as to meet the altered behavioral and metabolic requirements. Work in extreme cold requires fulfilling enhanced calorie needs. In high mountainous regions, cold combined with hypoxia produced loss of appetite and necessitated designing of special foods.     

Developmental,genetic, and environmental components of aerobic capacity at high altitude

The aerobic capacity of 268 subjects (158 males and 110 females) was evaluated in La Paz, Bolivia situated at 3,750 m. The sample included 1) 39 high altitude rural natives (all male); 2) 67 high altitude urban natives (32 male, 35 female); 3) 69 Bolivians of foreign ancestry acclimatized to high altitude since birth (37 male, 32 female); 4) 50 Bolivians of foreign ancestry acclimatized to high altitude during growth (25 male, 25 female); and 5) 43 non-Bolivians of either European or North American ancestry acclimatized to high altitude during adulthood (25 male, 18 female). Data analyses indicate that 1) high altitude urban natives, acclimatized to high altitude since birth or during growth, attained higher aerobic capacity than subjects acclimatized to high altitude during adulthood; 2) age at arrival to high altitude is inversely related to maximum oxygen consumption (V?O² max) expressed in terms L/min or ml/min/kg of lean body mass, but not in terms of ml/min/kg of body weight; 3) among subjects acclimatized to high altitude during growth, approximately 25% of the variability in aerobic capacity can be explained by developmental factors; 4) as inferred from evaluations of skin color reflectance and sibling similarities, approximately 20 to 25% of the variability in aerobic capacity at high altitude can be explained by genetic factors; 5) except among the non-Bolivians acclimatized to high altitude during adulthood, the aerobic capacity of individuals with high occupational activity level is equal to the aerobic capacity of high altitude rural natives; and 6) the relationship between occupational activity level and aerobic capacity is much greater among subjects acclimatized to high altitude before the age of 10 years than afterwards. Together these data suggest that the attainment of normal aerobic capacity at high altitude is related to both developmental acclimatization and genetic factors but its expression is highly mediated by environmental factors, such as occupational activity level and body composition. © 1995 Wiley-Liss, Inc.     

Effect of intermittent chronic exposure to hypoxia on feeding behaviour of rats

Healthy albino male rats were exposed to a simulated high altitude (HA) equivalent to 25000 ft (7620 m) for 6 h daily, continuously for 21 days to study the feeding behaviour. The 24-h food and water intake and body weight once in 3 days were recorded. Blood samples were drawn once a week from the retro-orbital venous plexus for blood sugar analysis. All the parameters were recorded before, during and after exposure to simulated HA. The results show a decrease in 24-h food and water intake and decreased gain in body weight during hypoxic exposure, which showed a tendency to come back to control during the post-exposure period. The blood sugar reflected a state of mild hyperglycaemia during exposure to HA.     

Morphological changes in the pituitary-adrenocortical axis in natives of La Paz

Increased activity of the hypothalamic-pituitary-adrenocortical axis is part of the response to the stress of initial exposure to hypoxia, but there is evidence to suggest that it persists after homeostatic stability has been regained and acclimatization achieved. The adrenal glands of five lifelong residents of La Paz, Bolivia, who had lived at altitudes in the range 3600–3800 m, were significantly larger than those in age-matched controls from sea level (15.3g vs 10.4g;P<0.001) and appeared hyperplastic. The pituitary glands of the highlanders were not significantly different in size from those of the controls (0.67 g vs 0.51 g), but contained larger populations of corticotrophs expressed in terms of the total cell population of their anterior lobes (25.6% vs 19.4%;P<0.001). In conjunction with other studies of this endocrine axis in man and animals exposed to a hypoxic environment, these data suggest that greater amounts of adrenocorticotrophic hormone (ACTH) are required to maintain normal adrenocortical function under such circumstances, probably as a result of hypoxic inhibition of adrenocortical sensitivity to stimulation. Physiological hyperplasia of the adrenal cortex may be common in people living at high altitude.     

Maximal exercise capacity in adolescent European and Amerindian high-altitude natives

Forty-seven highland natives were given maximal exercise tests on a treadmill ergometer at 3,600 m. The subjects were grouped into four subsamples on the basis of ethnicity (European vs. Aymara) and age (young vs. old adolescent). Two-way ANOVA indicated that VO2max adjusted for body size did not differ significantly between ethnic groups but was significantly larger in older than younger boys within each ethnic group (p less than .05). This finding does not support the hypothesis that Amerindian highland natives have adapted genetically to hypoxia but is consistent with the hypothesis that the relatively high VO2max's of highlanders are acquired by developmental adaptation. Several measures of ventilation and oxygen transport capacity differed significantly between ethnic groups, suggesting that growing European and Aymara boys may respond somewhat differently to the stress of high-altitude hypoxia. However, despite these differences, VO2max, an integrated measure of the overall functional capacity of the oxygen transport system, did not differ significantly between ethnic groups, suggesting that both groups are equally capable of meeting the body's oxygen requirements during maximal exercise at high altitude.     

Exposure to Intermittent High Altitude Induces Different Changes in Adenylyl Cyclase Activity in Hearts of Young and Adult Wistar Rats

Abstract

This study investigates changes of adenylyl cyclase activity in the heart of young and adult Wistar rats exposed to experimental conditions simulating high altitude hypoxia as a model for interpretation of some adaptive changes of adenylyl cyclase observed in human. The exposure of rats to intermittent high altitude (IHA) hypoxia (5000 m) showed significant adaptive changes. The right ventricular weight and the ratio of right/left ventricular weights of adult rats exposed to IHA were significantly increased when compared to appropriate controls; adaptive changes of cardiac adenylyl cyclase being dependent on the age of the animals. The isoprenaline‐stimulated activity was higher in the left than in the right ventricle, and in both ventricles it was higher in young rats than in adult rats. When compared to controls, isoprenaline stimulation was decreased in the right ventricles of adapted young rats and, by contrast, it was increased in the left ventricles of adapted adult rats. This decrease and increase of adenylyl cyclase activity evoked by isoprenaline was paralleled by forskolin‐induced adenylyl cyclase activity in these experimental groups. It seems therefore that the changes in the pattern of total adenylyl cyclase activity observed under IHA hypoxia may at least be partially explained by the changes of beta‐adrenergic receptor susceptibility following IHA hypoxia.     

Growth trends among male Bods of Ladakh--a high altitude population

A random sample of 274 native male Bods of Ladakh ranging in age from 11 to 19 years, living in Leh (Ladakh) at mean altitude of 3,514 metres, was studied. The pattern of growth of this sample was compared with the sea level Indians. The results indicate that: (1) The so called adolescent spurt is not well defined among Bod highlanders. (2) Bods grow faster than plain dwelling Indians and are taller and heavier at the age of 19 years. (3) The highlanders exhibit greater chest circumference than the lowland norms. This finding, similar to those among Andean natives, supports high altitude hypoxia's role in human growth and morphology.     

不同海拔高原适应相关肝脏功能与脂代谢变化

目的：分析高原移居者肝脏功能及血脂水平。方法：选择不同海拔高原移居者（平均10年以上）男性80名,无高血压及糖尿病病史。按高原会议订立标准分组：低海拔组（〈1500米）8例,中海拔组（1500-2500米）9例,高海拔组（2500-4500米）36例,特高海拔及以上组（〉4500米）9例,运输组（2700-4600米）18例。清晨抽取空腹静脉血5mL,Roche Modular PE全自动生化免疫分析仪检测肝脏功能及血脂水平。结果：高海拔移居者,总胆红素和直接胆红素升高,总胆固醇、低密度脂蛋白降低;特高海拔及以上移居者（〉4500米）,直接胆红素升高,总胆固醇、低密度脂蛋白、载脂蛋白B降低。结论：本文研究结果提示了,高原缺氧环境下,肝脏自身功能抗缺氧发生改变或高原饮食受限可引起肝脏功能变化,进而影响脂类代谢,是机体对长期乏氧状态的适应性改变。     

Mitochondrial DNA analysis in Tibet: Implications for the origin of the Tibetan population and its adaptation to high altitude

Mitochondrial DNAs (mtDNAs) of 54 Tibetans residing at altitudes ranging from 3,000–4,500 m were amplified by polymerase chain reaction (PCR), examined by high-resolution restriction endonuclease analysis, and compared with those previously described in 10 other Asian and Siberian populations. This comparison revealed that more than 50% of Asian mtDNAs belong to a unique mtDNA lineage which is found only among Mongoloids, suggesting that this lineage most likely originated in Asia at an early stage of the human colonization of that continent. Within the Tibetan mtDNAs, sets of additional linked polymorphic sites defined seven minor lineages of related mtDNA haplotypes (haplogroups). The frequency and distribution of these haplogroups in modern Asian populations are supportive of previous genetic evidence that Tibetans, although located in southern Asia, share common ancestral origins with northern Mongoloid populations. This analysis of Tibetan mtDNAs also suggests that mtDNA mutations are unlikely to play a major role in the adaptation of Tibetans to high altitudes. © 1994 Wiley-Liss, Inc.     

Effect of beta-adrenergic blockade on plasma lactate concentration during exercise at high altitude

When unacclimatized lowlanders exercise at high altitude, blood lactate concentration rises higher than at sea level, but lactate accumulation is attenuated after acclimatization. These responses could result from the effects of acute and chronic hypoxia on beta-adrenergic stimulation. In this investigation, the effects of beta-adrenergic blockade on blood lactate and other metabolites were studied in lowland residents during 30 min of steady-state exercise at sea level and on days 3, 8, and 20 of residence at 4300 m. Starting 3 days before ascent and through day 15 at high altitude, six men received propranolol (80 mg three times daily) and six received placebo. Plasma lactate accumulation was reduced in propranolol- but not placebo-treated subjects during exercise on day 3 at high altitude compared to sea-level exercise of the same percentage maximal oxygen uptake (VO2max). Plasma lactate accumulation exercise on day 20 at high altitude was reduced in both placebo- and propranolol-treated subjects compared to exercise of the same percentage VO2max performed at sea level. The blunted lactate accumulation during exercise on day 20 at high altitude was associated with reduced muscle glycogen utilization. Thus, increased plasma lactate accumulation in unacclimatized lowlanders exercising at high altitude appears to be due to increased beta-adrenergic stimulation. However, acclimatization-induced changes in muscle glycogen utilization and plasma lactate accumulation are not adaptations to chronically increased beta-adrenergic activity.     

Mast cells in the human lung at high altitude

Mast cell densities in the lung were measured in five native highlanders of La Paz (3600 m) and in one lowlander dying from high-altitude pulmonary oedema (HAPO) at 3440 m. Two of the highlanders were mestizos with normal pulmonary arteries and the others were Aymara Indians with muscular remodelling of their pulmonary vasculature. The aim of the investigation was to determine if accumulation of mast cells in the lung at high altitude (HA) is related to alveolar hypoxia alone, to a combination of hypoxia and muscularization of the pulmonary arterial tree, or to oedema of the lung. The lungs of four lowlanders were used as normoxic controls. The results showed that the mast cell density of the two Mestizos was in the normal range of lowlanders (0.6–8.8 cells/mm²). In the Aymara Indians the mast cell counts were raised (25.6–26.0 cells/mm²). In the lowlander dying from HAPO the mast cell count was greatly raised to 70.1 cells/mm² lung tissue. The results show that in native highlanders an accumulation of mast cells in the lung is not related to hypoxia alone but to a combination of hypoxia and muscular remodelling of the pulmonary arteries. However, the most potent cause of increased mast cell density in the lung at high altitude appears to be high-altitude pulmonary oedema.     

Optimal birthweights in Peruvian populations at high and low altitudes

This study tests the hypothesis that optimum birthweight for survival is lower among hospital-born infants in Puno, Peru (altitude 3860 m) than that among their counterparts at low altitude in Tacna, Peru (altitude 600 m). The data are derived from hospital birth records for 1971 and 1972 and municipal death records for 1971 through 1973. Linking these records permits analysis of the patterns of mortality in relation to birthweight. Stabilizing selection upon birthweight is operating in both populations. The high altitude population has a lower mean birthweight and a lower optimal birthweight. The Puno population is closer to its optimal birthweight distribution and, as a result of mortality during infancy, is approaching its optimum birthweight distribution for survival more rapidly than the Tacna population. It appears that the high altitude Puno population may well be adapted to its environment in the sense that there is less selective mortality on birthweight phenotypes.     

Biochemical mechanisms of red blood cell 2,3-diphosphoglycerate increase at high altitude

Red blood cell 2,3 diphosphoglycerate (2,3-DPG) levels increase after ascent to high altitude. Studies were undertaken to identify the biochemical mechanisms responsible for eliciting the 2,3-DPG response in several types of subjects. These included (1) short-term exposure to 3400 m in ten subjects; (2) exposure to 4300 m in an additional ten subjects; (3) studies in 28 high-altitude normal residents of 3100 m; and (4) studies in 28 high-altitude residents with chronic mountain polycythemia. Controls were 41 residents of 240 m. Regression analysis identified the glycolytic variables, termed “key variables,” on which variation in 2,3-DPG levels was dependent (P < .05). Key variables common to the short-term studies were glucose-6-phosphate, phosphoenolpyruvate, and the ratio of the levels of adenosine diphosphate to adenosine triphosphate. The positions of these key variables in the glycolytic pathway and their mean levels suggest erythrocyte hexokinase and pyruvate kinase activation as possible enzymatic mechanisms. Key variables unique to the 3400 m study suggested phosphofructokinase activation also acted to increase 2,3-DPG levels. 2,3-DPG levels in the normal 3100 m residents were not different from low-altitude values, and 2,3-DPG levels in these samples did not appear to be dependent on any of the glycolytic variables examined. Among the high-altitude residents with polycythemia, higher 2,3-DPG levels were dependent on glucose-6-phosphate, fructose diphosphate, dihydroxyacetone phosphate, and the ratio of adenosine diphosphate to adenosine triphosphate levels. The positions of these variables in the glycolytic pathway and their mean levels suggested activation of the hexokinase and phosphofructokinase enzymes.     

The pulmonary circulation of some domestic animals at high altitude

Pulmonary haemodynamics and the histology of the pulmonary vasculature have been studied at high altitude in the yak, in interbreeds between yaks and cattle, and in domestic goats and sheep indigenous to high altitudes together with crosses between them and low-altitude strains. Cattle at high altitude had a higher pulmonary arterial pressure than cattle at low altitude. The yak and two interbreeds with cattle (dzos and stols) had a low pulmonary arterial pressure compared with cattle, while the medial thickness of the small pulmonary arteries was less than would be expected in cattle, suggesting that the yak has a low capacity for hypoxic pulmonary vasoconstriction and that this characteristic is transmitted genetically. Goats and sheep showed haemodynamic evidence of a limited response of the pulmonary circulation to high altitude, but no evidence that the high altitude breeds had lost this response. There were no measurable differences in the thickness of the media of the small pulmonary arteries between high- and low-altitude breeds of goats and sheep. All these species showed prominent intimal protrusions of muscle into the pulmonary veins but no specific effect of high altitude in this respect.     

Metabolic responses during initial days of altitude acclimatization in the Eastern Himalayas

The study was carried out on 16 men (aged 20–30 years) to evaluate daily metabolic responses during the early phase of altitude acclimatization at moderate altitudes between 3100 and 4200 m in the Eastern Himalayas. Resting (R) and submaximal exercise (E) oxygen consumption (|VO₂) at 100 W at sea level (SL) were 3.25 (SEM 0.15) and 20.31 (SEM 0.77) ml/kg per min respectively. On day 1 at 3110 m both R and E |VO₂ decreased (P<0.001) and subsequently remained constant. At 3445 m these values tended to increase over the 3110 m values but were lower than the SL values. At 4177 m the decline in |VO₂ was significantly greater (P<0.01) than at the preceding altitudes. Pulmonary ventilation (|VE) increased consistently (P<0.001) with increase in altitude. The arterial oxygen saturation (S _a O₂) at different altitudes was lower (P<0.001) than SL values. The cardiac frequency (f _C ) at R and E was higher (P<0.001) at altitude; the values at 3110 and 3445 m were significantly lower (P<0.001) than at 4177 m. Blood pressure (BP) increased (P<0.001) on the first day at each altitude. The systolic BP tended to decline towards SL values but the diastolic BP remained high (P<0.001) throughout. The resting blood lactic acid concentration, [la ^–] _bl , showed a decline (P<0.001) only at 4177 m. The [la ^–] _bl at E was similar at 3110 and 3445 m but was higher (P<0.01) at 4177 m. These observations suggest that acclimatization to a mid-altitude of 3445 m can be safely avoided where rapid ascent to higher altitude is required.     

Comparison of muscle force,muscle endurance,and electromyogram activity during an expedition at high altitude

Handgrip force (HF), maximal pinch force (MF), muscle endurance (ME), and the median power frequency (MdPF) of the activity shown in the electromyogram (EMG) were studied at various altitudes in eight normal healthy subjects. MF and ME were measured between the index finger and thumb, and all measurements were obtained at altitudes ranging from 610 to 4860 m during an expedition in the Qinghai Plateau in China. With the change in altitude HF, ME, and MF showed no significant change. Compared to the MdPF at 2260 m on ascent, the MdPF at other altitudes showed a significant decrease (P<0.01). Thus, we conclude that muscle performance (HF, MF, and ME) was not affected by the environment at high altitude. However, MdPF was affected and the mean MdPF at 610 m after the expedition did not recover to initial values of MdPF. We suggest these results may have been affected by fatigue and chronic exposure to the hypobaric hypoxic environment, since the members of the expedition party expressed feelings of sluggishness and fatigue after the expedition.