Search

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

For the male inhabitants of La Paz, Bolivia (3200-4100 m), and other high altitude regions in America and Asia, chronic mountain sickness (CMS) is a major health problem. Since CMS was first described by Carlos Monge in the Peruvian Andes in 1925, numerous research papers have been devoted to this topic, but many unanswered questions still exist with respect to the beginning of the disease and its cause(s). The experience with CMS has shown that an excessively high hemoglobin concentration is not favorable for high altitude acclimatization, and the hypothesis of theoretically "optimal" hematocrit and "optimal" hemoglobin has been made. The calculated optimal hemoglobin concentration of 14.7 g/dL for resting men in the Andes is discussed as theoretical and not applicable in real life. The most frequent congenital and acquired heart diseases are discussed, such as patent ductus, atrial septum defect, ventricle septum defect among congenital heart diseases and the still very frequent rheumatic valve cardiopathies and Chagas disease as acquired cardiopathies. Among the typical acquired heart diseases of the high altitude dweller, special attention is given to chronic cor pulmonale as a consequence of severe CMS with pulmonary hypertension.

This study tested the hypothesis that Andean natives are adapted to high altitude (HA) via high work efficiency during exercise in hypoxia. A total of 186 young males and females were tested in Bolivia, comprising eight different subject groups. Groups were identified based on gender, ancestry (Aymara vs. European), altitude of birth (highlands vs. lowlands), and the altitude where tested (420, 3600, 3850 m). This design allows partitioning of ancestral (i.e., genetic) and developmental effects. To minimize measurement error, subjects were given two submaximal exercise tests on a cycle ergometer (on separate days). Each test consisted of four 5-min work bouts (levels), each separated by a 5-min rest period. For all groups, the oxygen consumption (V(O2))-work rate relationship was not different from the sea-level reference. Gross and net efficiencies (GE and NE) were not different between groups at any work level, with the exception of European men born in the lowlands and acclimatized and tested at 3600 m. These men showed slightly lower V(O2) at high work output, but this may be due to a nonsteady-state V(O2) kinetic, rather than to an altered steady-state V(O2)-work rate relationship per se. There were no significant group differences in delta efficiency (DE). In sum, these results provide no support for the hypothesis of energetic advantage during submaximal work in Andean HA natives. A review and analysis of the literature suggest that the same is true for HA natives in the Himalayas.

We developed a simple, non-invasive, and affordable method for estimating net energy expenditure (EE) in children performing activities at high altitude. A regression-based method predicts net oxygen consumption (VO(2)) from net heart rate (HR) along with several covariates. The method is atypical in that, the "net" measures are taken as the difference between exercise and resting VO(2) (DeltaVO(2)) and the difference between exercise and resting HR (DeltaHR); DeltaVO(2) partially corrects for resting metabolic rate and for posture, and DeltaHR controls for inter-individual variation in physiology and for posture. Twenty children between 8 and 13 years of age, born and raised in La Paz, Bolivia (altitude 3,600m), made up the reference sample. Anthropometric measures were taken, and VO(2) was assessed while the children performed graded exercise tests on a cycle ergometer. A repeated-measures prediction equation was developed, and maximum likelihood estimates of parameters were found from 75 observations on 20 children. The final model included the variables DeltaHR, DeltaHR(2), weight, and sex. The effectiveness of the method was established using leave-one-out cross-validation, yielding a prediction error rate of 0.126 for a mean DeltaVO(2) of 0.693 (SD 0.315). The correlation between the predicted and measured DeltaVO(2) was r = 0.917, suggesting that a useful prediction equation can be produced using paired VO(2) and HR measurements on a relatively small reference sample. The resulting prediction equation can be used for estimating EE from HR in free-living children performing habitual activities in the Bolivian Andes.

SUMMARY At sea level normally menstruating women show increased ventilation (V̇e) and hemodynamic changes due to increased progesterone (P) and estrogen (E2) levels during the mid-luteal (L) compared to the mid-follicular (F) phase of the ovarian cycle. Such changes may affect maximal exercise performance. This repeated-measures, randomized study, conducted at 3600 m, tests the hypothesis that a P-mediated increase in V̇e increases maximal oxygen consumption (V̇O2max) during the L phase relative to the F phase in Bolivian women, either born and raised at high altitude (HA), or resident at HA since early childhood. Subjects (N=30) enrolled in the study were aged 27.7±0.7 years (mean ± s.e.m.) and non-pregnant, non-lactating, relatively sedentary residents of La Paz, Bolivia, who were not using hormonal contraceptives. Mean salivary P levels at the time of the exercise tests were 63.3 pg ml–1 and 22.9 pg ml–1 for the L and F phases, respectively. Subset analyses of submaximal (N=23) and maximal (N=13) exercise responses were conducted only with women showing increased P levels from F to L and, in the latter case, with those also achieving true V̇O2max. Submaximal exercise V̇e and ventilatory equivalents were higher in the L phase (P

Peak oxygen consumption (VO2peak) was measured in 150 adult males (18–35 years old) in Bolivia, using a complete migrant study design to partition developmental from ancestral (genetic) effects of high-altitude (HA) exposure. High-altitude natives (HANs, Aymara/Quechua ancestry, n = 75) and low-altitude natives (LANs, European/North American ancestry, n = 75) were studied at high altitude (3,600–3,850 m) and near sea level (420 m). HAN and LAN migrant groups to a nonnative environment were classified as: multigeneration migrants, born and raised in a nonnative environment; child migrants who migrated to the nonnative environment during the period of growth and development (0–18 years old); and adult migrants who migrated after 18 years of age. Variability in VO2peak due to high-altitude adaptation was modeled by covariance analysis, adjusting for fat-free mass and physical activity (training) differences between groups. A trend for increased VO2peak with increasing developmental high-altitude exposure in migrant groups did not reach statistical significance, but low statistical power may have limited the ability to detect this effect. HANs and LANs born, raised, and tested at high altitude had similar VO2peak values, indicating no genetic effect, or an effect much smaller than that reported previously in the literature. There was no functional correlation between forced vital capacity and VO2peak, within or across groups. These results do not support the hypothesis that Andean HANs have been selected to express a greater physical work capacity in hypoxia. Am J Phys Anthropol 110:435–455, 1999. © 1999 Wiley-Liss, Inc.

The aim of this work was to evaluate the effects of high altitude and low socioeconomic status (SES) on aerobic and anaerobic power in 11-yr-old Bolivian girls. At both high (3,600 m) and low (420 m) altitudes, low-SES groups of girls were compared to similarly aged, high-SES girls. At low altitude, low-SES girls were also compared with younger high-SES girls with the same anthropometric characteristics. Anthropometric data were similar between high-SES and low-SES girls at both altitudes, but low-SES girls showed a 9-mo growth delay. Maximal O2 uptake was significantly lower for low-SES girls at both altitudes. Values did not differ when expressed relative to body weight at high altitude for high-SES vs. low-SES girls (37.6 +/- 1.2 vs. 39.3 +/- 1.0 ml.min-1.kg body wt-1), but a difference persisted at low altitude between high- and low-SES girls (37.5 +/- 1.0 vs. 34.7 +/- 0.7 ml.min-1.kg body wt-1). Anaerobic power (Pmax, force-velocity test; Pwing, Wingate test) was reduced for low-SES girls at both altitudes, whatever the mode of expression. For a given SES, the relative anaerobic performances were lower at low altitude. At low altitude, low-SES girls developed lower anaerobic power than did younger high-SES girls with similar anthropometric characteristics. In conclusion, at both altitudes, the reduction of anaerobic performances observed in girls of low SES could not be totally explained by anthropometric factors. Structural and/or functional muscle alterations are suggested. Moreover, at low altitude, tropical and other factors may have contributed to differences in performance between low- and high-SES girls.

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) 42 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 (VO2 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.

The leaves of the coca plant (Erythroxylum sp.) have long been chewed by natives of the highland Andes. Folk belief is that the mild stimulant effect is indispensable as an ergogenic aid for strenuous work activities in a high altitude environment. This study explored the exercise responses of 23 nonhabitual coca chewing males who were asked to pedal a bicycle ergometer through a series of submaximal and maximal workloads both with and without coca chewing. The protocol of the exercise test was specifically designed to allow for the determination of work and muscular efficiencies during to submaximal work. The subjects showed no differences between the coca and control work protocols for VO2 max (1/min), VCO2 max (1/min), or maximal work output (watts). Further, there were no differences between coca and control work protocols in oxygen saturation (%), pulmonary ventilation (1/min), or respiratory exchange ratio (VCO2 /VO2 ) at any level of work. Coca chewing caused subjects to have a higher heart rate (bpm) and lower oxygen pulse (ml/beat) for most submaximal workloads and higher ventilatory equivalents (VE/VO2 and VE/VCO2 ) above 50% of VO2 max. Although there was a tendency for higher gross efficiencies (GE) during the coca exercise test at lower relative work levels, between 30-40% of the VO2 max, this difference did not reach significance. Mean net efficiency (NE) was higher (P=0.018) at a relative work level of ∼32% of the VO2 max for exercise with coca (23.2% vs. 20.8%). This difference was not apparent at any other work level. The mean delta efficiency (DE) was significantly lower (P = 0.012) for exercise with coca (26.7%) than for exercise without coca (28.2%). These efficiency differences suggest a muscle metabolic effect for coca chewing at low workloads whereby less oxygen is consumed by the muscle to perform a given work task. Howeve, given the difficulty of interpreting efficiency values, it is not entirely clear if the differences are indicative of a work performance benefit for coca chewing. © 1995 Wiley-Liss, Inc.

The aim of this study was to analyze the effect of altitude and socioeconomic status on the maximal oxygen uptake (VO2max) of prepubertal Bolivian boys. The subjects were 143 prepubertal boys (10 to 11.5 years old) living in La Paz (altitude 3600 m, n = 67) and Santa Cruz de la Sierra (altitude 420m, n = 76). At high altitude, 23 boys were from a high socioeconomic status (HAHSES) and 44 from a low socioeconomic background (HALSES). At low altitude, 29 boys were from a high socioeconomic level (LAHSES) and 47 from a low socioeconomic background (LALSES). Anthropometric characteristics were determined in order to assess the physical growth of the boys. The VO2max was determined from a progressive maximal exercise (direct method). The subjects performed this test using the same cycle ergometer at both high and low altitudes. For the overall anthropometric parameters, there was no significant difference between highland and lowland boys of the same socioeconomic status. However, regardless of altitude, boys from a low socioeconomic background were 2 years behind those from a high socioeconomic background. There was no significant difference for VO2max between boys from high and low socioeconomic backgrounds at HA (HAHSES: 37.2 +/- 5.6; HALSES: 38.9 +/- 6.4 ml.min-1.kg-1 body weight) and at LA (LAHSES: 42.6 +/- 5.4; LALSES: 43.1 +/- 4.9 ml.min-1.kg-1 body weight). The VO2max of highland boys was, on average, 11% lower than that of lowland boys. It appears, therefore, that a difference in socioeconomic status has no effect on the VO2max (ml.min-1.kg-1) of prepubertal children at low altitude as well as the altitude of 3600m.

The aim of this work was to study the effect of hypoxic stress on the physical growth of prepubertal Bolivian boys (10-11.5 years of age) of the same socioeconomic and nutritional conditions. The subjects consisted of 143 boys living in La Paz (altitude 3600 m, n = 67) and Santa Cruz de la Sierra (altitude 420 m, n = 76). Among the boys studied at high altitude, 23 were from a high socioeconomic background (HA1) and 44 from a low socioeconomic background (HA2). The group studied at low altitude consisted of 47 boys from a high socioeconomic background (LA1) and 29 from a low socioeconomic background (LA2). A scientific evaluation of the nutritional status of the boys was realized from specific anthropometric characteristics (height, body weight, upper arm muscle circumference, body fat mass and body mass index) and haematological (haematocrit, haemoglobin, serum iron, serum ferritin, red cell protoporphyrin, transferrin saturation) and biochemical (total serum protein, albumin and prealbumin) parameters. At high as at low altitudes, the biometric characteristics of boys from a low socioeconomic background were significantly lower than those of boys from a high socioeconomic background. The physical growth of HA2 and LA2 boys was delayed by approximately 2 years. All the boys had biochemical and haematological parameters within the normal range. Boys from a low socioeconomic background were considered as marginally undernourished and those from a high socioeconomic background as well-nourished. Within the same socioeconomic class there was no nutritional difference between highland and lowland boys. Similarly, and this is the most important feature of this study, there was no difference for the overall biometric characteristics between highland and lowland boys of the same socioeconomic and nutritional status. Therefore, it appears that when socioeconomic and nutritional conditions are taken into account, there is no effect of hypoxic stress on the physical growth of prepubertal Andean highland boys.

Field tests of running and laboratory tests were performed in La Paz [high altitude (HA), 3700 m] and in Clermont-Ferrand [low altitude (LA), 300 m] to investigate their validity at HA. Prepubertal boys of mean ages 10.6 years (HA1,n = 16; LA1,n = 28) and pubertal boys of 13.7 years (HA2,n = 12; LA2,n = 41) took part in the study. All the boys performed a 30-m sprint (v30m), a 30-s shuttle run (v3os) and a progressive shuttle run test until their maximal aerobic velocity (vmaxsRT). Maximal oxygen consumption was extrapolated from the last test.\(\left( {\dot VO_{2maxSRT} } \right)\). In the laboratory, the boys performed a force-velocity test (Pmax), a Wingate test (PWing) and a graded test to measure maximal oxygen consumption\(\left( {\dot VO_{2maxB} } \right)\); direct method) on a cycle ergometer. At similar ages, there was no significant difference between HA and LA boys forv30m andPmax. Thev30s of HA boys was 3%–4% lower than those of LA boys (P

In Bolivia, malnutrition in children is a major health problem that may be caused by inadequate protein, energy, and micronutrient intake; exposure to bacterial and parasitic infections; and life in a multistress environment (high altitude, cold, cosmic radiation, low ambient humidity). However, no data on protein absorption and utilization at high altitude were available. Therefore, we evaluated the effect of altitude on protein metabolism in Bolivian children. We measured protein utilization using leucine labeled with a stable isotope ((13)C) in two groups of healthy prepubertal children matched for age. Group 1 (n = 10) was examined at high altitude (HA) in La Paz (3600 m), and group 2 (n = 10) at low altitude (LA) in Santa Cruz (420 m). The nutritional status did not differ between groups but, as was to be expected, the HA group had higher hemoglobin concentration than the LA group. The children consumed casein that was intrinsically labeled with L-(1-(13)C) leucine and expired (13)CO(2) was analyzed. Samples of expired air were measured by isotope ratio mass spectrometer in Clermont-Ferrand. It was found that cumulative leucine oxidation ((13)CO(2)) at 300 min after ingestion was 19.7 +/- 4.9% at HA and 25.2 +/- 3.2% at LA. These results showed that protein absorption and/or utilization is significantly affected by altitude.

Pulmonary gas exchange and acid-base state were compared in nine Danish lowlanders (L) acclimatized to 5,260 m for 9 wk and seven native Bolivian residents (N) of La Paz (altitude 3,600–4,100 m) brought acutely to this altitude. We evaluated normalcy of arterial pH and assessed pulmonary gas exchange and acid-base balance at rest and during peak exercise when breathing room air and 55% O2. Despite 9 wk at 5,260 m and considerable renal bicarbonate excretion (arterial plasma HCO3 − concentration = 15.1 meq/l), resting arterial pH in L was 7.48 ± 0.007 (significantly greater than 7.40). On the other hand, arterial pH in N was only 7.43 ± 0.004 (despite arterial O2 saturation of 77%) after ascent from 3,600–4,100 to 5,260 m in 2 h. Maximal power output was similar in the two groups breathing air, whereas on 55% O2only L showed a significant increase. During exercise in air, arterial Pco 2 was 8 Torr lower in L than in N ( P < 0.001), yet Po 2 was the same such that, at maximal O2 uptake,alveolar-arterial Po 2 difference was lower in N (5.3 ± 1.3 Torr) than in L (10.5 ± 0.8 Torr), P = 0.004. Calculated O2 diffusing capacity was 40% higher in N than in L and, if referenced to maximal hyperoxic work, capacity was 73% greater in N. Buffering of lactic acid was greater in N, with 20% less increase in base deficit per millimole per liter rise in lactate. These data show in L persistent alkalosis even after 9 wk at 5,260 m. In N, the data show 1) insignificant reduction in exercise capacity when breathing air at 5,260 m compared with breathing 55% O2; 2) very little ventilatory response to acute hypoxemia (judged by arterial pH and arterial Pco 2 responses to hyperoxia); 3) during exercise, greater pulmonary diffusing capacity than in L, allowing maintenance of arterial Po 2despite lower ventilation; and 4) better buffering of lactic acid. These results support and extend similar observations concerning adaptation in lung function in these and other high-altitude native groups previously performed at much lower altitudes.

Chest depth, chest width, forced vital capacity (FVC), and forced expiratory volume (FEV1) were measured in 170 adult males differing by ancestral (genetic) and developmental exposure to high altitude (HA). A complete migrant study design was used to study HA natives (Aymara/Quechua ancestry, n = 88) and low altitude (LA) natives (European/North American ancestry, n = 82) at both altitude (La Paz, Bolivia, 3,600 m) and near sea level (Santa Cruz, Bolivia, 420 m). HAN and LAN migrant groups were classified as: N(th) generation migrants, born and raised in a non-native environment; child migrants who migrated during the period of growth and maturation (0-18 yrs); and adult migrants who migrated after 18 years of age. Chest depth, FVC, and FEV1 measures were larger with increasing developmental exposure in both HAN migrants at LA and LAN migrants at HA. Developmental responses were similar between HAN and LAN groups. FVC and FEV1 measures were larger in HANs vs LANs born and raised at HA to suggest a genetic effect, but were similar in HANs and LANs born and raised at LA. The similarity of HAN and LAN groups at LA suggests that the genetic potential for larger lung volumes at HA depends upon developmental exposure to HA. Additional data for females (HANs at HA, n = 20, and LAN adult migrants to HA, n = 17) show similar differences as those shown between male HAN and LAN groups. Am. J. Hum. Biol. 11:383-395, 1999. Copyright 1999 Wiley-Liss, Inc.

Arterial oxygen saturation (SaO2) was measured at 3,600–3,850 m by pulse oximetry at rest and during submaximal exercise in three study groups: 1) highland Aymara natives of the Bolivian altiplano (n = 25); 2) lowland European/North American sojourners to the highlands with at least 2 months of acclimatization time to 3,600 m (n = 27); and 3) subjects of European ancestry born and raised at 3,600 m (n = 22). Aymara subjects maintained ∼1 percentage point higher SaO2 during submaximal work up to 70% of their maximal work capacity, and showed a smaller rate of decline in SaO2 with increasing work compared to both European study groups. The higher-exercise SaO2 of Aymara compared to Europeans born and raised at 3,600 m suggests genetic adaptation. The two European study groups, who differed by exposure to high altitude during their growth and development period, did not show any significant difference in either resting or exercise SaO2. This suggests that the developmental mode of adaptation is less important than the genetic mode of adaptation in determining exercise SaO2. A weak correlation was detected (across study groups only) between the residual forced vital capacity (FVC) and the residual SaO2 measured at the highest level of submaximal work output (P = 0.024, R = 0.26). While firm conclusions based on this correlation are problematic, it is suggested that a part of the higher SaO2 observed in Aymara natives is due to a larger lung volume and pulmonary diffusion capacity for oxygen. Results from this study are compared to similar studies conducted with Tibetan natives, and are interpreted in light of recent quantitative genetic analyses conducted in both the Andes and Himalayas. Am J Phys Anthropol 113:169–181, 2000. © 2000 Wiley-Liss, Inc.

The effect of chronic hypoxia on gender differences in physiology and neurochemistry of chemosensory pathways was studied in prepubertal and adult rats living at sea level (SL; Lyon, France) or at high altitude (HA; La Paz, Bolivia, 3,600 m). HA adult rats had higher hematocrit (Ht%), Hb concentration, resting ventilatory rate (Ve100), and higher tyrosine hydroxylase (TH) activity in carotid bodies (CB) than SL animals. At HA and SL, adult females had lower Ht% (46.0 ± 0.8 vs. 50.4 ± 0.6% at HA, P < 0.05 and 43.8 ± 0.9 vs. 47.1 ± 0.8% at SL, P < 0.05) and Hb (16.1 ± 0.3 vs. 17.7 ± 0.2 g/dl at HA, P < 0.05 and 14.5 ± 0.3 vs. 15.6 ± 0.1 g/dl at SL, P < 0.05) than males. Females had higher Ve100 [170 ± 19 vs. 109 ± 7 ml ⋅ min− 1 ⋅ 100 g− 1 at HA, P < 0.05 and 50 ± 3 vs. 40 ± 2 ml ⋅ min− 1 ⋅ 100 g− 1 at SL, not significant (NS)] and lower CB-TH activity (1.40 ± 0.2 vs. 3.87 ± 0.6 pmol/20 min at HA, P < 0.05 and 0.52 ± 0.1 vs. 0.68 ± 0.1 pmol/20 min at SL; NS) than males at HA only. The onset of hypoxic ventilatory response during development was delayed at HA. Prepubertal HA females had higher Ve100 than males (2 wk old, +47%) and higher CB-TH activity (3 wk old, +51%). Medullary noradrenergic groups were sex dimorphic during development at SL. Rats raised at HA had a drop of TH activity between the second and the third postnatal week in all medullary groups. In conclusion, our data support the hypothesis that the CB is the major site for sexual differentiation of the ventilatory control. Ventilatory differences appeared before puberty, and the animals bred at HA had profound alterations in the developmental process of the chemoreflex and its neural pathways. Some of these alterations are under dependence of the sex of the animal, and there is an important interaction between gender and the hypoxic environmental condition during the developmental period.

Kayser, Bengt, Roland Favier, Guido Ferretti, Dominique Desplanches, Hilde Spielvogel, Harry Koubi, Brigitte Sempore, and Hans Hoppeler. Lactate and epinephrine during exercise in altitude natives. J. Appl. Physiol. 81(6): 2488–2494, 1996.—We tested the hypothesis that the reported low blood lactate accumulation ([La]) during exercise in altitude-native humans is refractory to hypoxia-normoxia transitions by investigating whether acute changes in inspired O2 fraction ([Formula: see text]) affect the [La] vs. power output (W˙) relationship or, alternatively, as reported for lowlanders, whether changes in [La] vs. W˙ on changes in[Formula: see text] are related to changes in blood epinephrine concentration ([Epi]). Altitude natives [ n = 8, age 24 ± 1 (SE) yr, body mass 62 ± 3 kg, height 167 ± 2 cm] in La Paz, Bolivia (3,600 m) performed incremental exercise with two legs and one leg in chronic hypoxia and acute normoxia (AN). Submaximal one- and two-leg O2 uptake (V˙o 2) vs.W˙ relationships were not altered by[Formula: see text]. AN increased two-leg peak V˙o 2 by 10% and peakW˙ by 7%. AN paradoxically decreased one-leg peak V˙o 2 by 7%, whereas peak W˙ remained the same. The [La] vs. W˙ relationships were similar to those reported in unacclimatized lowlanders. There was a shift to the right on AN, and maximum [La] was reduced by 7 and 8% for one- and two-leg exercises, respectively. [Epi] and [La] were tightly related (mean r = 0.81) independently of[Formula: see text]. Thus normoxia attenuated the increment in both [La] and [Epi] as a function of W˙, whereas the correlation between [La] and [Epi] was unaffected. These data suggest loose linkage of glycolysis to oxidative phosphorylation under influence from [Epi]. In conclusion, high-altitude natives appear to be not fundamentally different from lowlanders with regard to the effect of acute changes in[Formula: see text] on [La] during exercise.

Desplanches, D., H. Hoppeler, L. Tüscher, M. H. Mayet, H. Spielvogel, G. Ferretti, B. Kayser, M. Leuenberger, A. Grünenfelder, and R. Favier. Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia. J. Appl. Physiol. 81(5): 1946–1951, 1996.—Twenty healthy high-altitude natives, residents of La Paz, Bolivia (3,600 m), participated in 6 wk of endurance exercise training on bicycle ergometers, 5 times/wk, 30 min/session, as previously described in normoxia-trained sea-level natives (H. Hoppeler, H. Howald, K. E. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. R. Weibel. J. Appl. Physiol. 59: 320–327, 1985). A first group of 10 subjects was trained in chronic hypoxia (HT; barometric pressure = 500 mmHg; inspired O2fraction = 0.209); a second group of 10 subjects was trained in acute normoxia (NT; barometric pressure = 500 mmHg; inspired O2fraction = 0.314). The workloads were adjusted to ∼70% of peak O2consumption (V˙o2 peak) measured either in hypoxia for the HT group or in normoxia for the NT group.V˙o2 peakdetermination and biopsies of the vastus lateralis muscle were taken before and after the training program.V˙o2 peakin the HT group was increased (14%) in a way similar to that in NT sea-level natives with the same protocol. Moreover,V˙o2 peakin the NT group was not further increased by additional O2delivery during the training session. HT or NT induced similar increases in muscle capillary-to-fiber ratio (26%) and capillary density (19%) as well as in the volume density of total mitochondria and citrate synthase activity (45%). It is concluded that high-altitude natives have a reduced capillarity and muscle tissue oxidative capacity; however, their training response is similar to that of sea-level residents, independent of whether training is carried out in hypobaric hypoxia or hypobaric normoxia.

The effect of acute hypoxia (FIO2 = 0.137 +/- 0.001) at Low Altitude (LA: Clermont-Ferrand, 330 m) and acute normoxia (FIO2 = 0.306 +/- 0.006) at High Altitude (HA: La Paz, 3600 m) on performance during a 30-s Wingate test has been investigated in prepubertal children (Tanner stage 1). Twenty five boys (LA, n = 10; HA, n = 15) aged from 10.6 to 12.7 years performed two Wingate tests at random: at LA, one in normoxia (ambient air) and one in acute hypoxia and at HA, one in chronic hypoxia (ambient air) and one in acute normoxia. The subjects performed the two tests using the same calibrated cycle ergometer. Peak Power (PP), Mean Power (MP), O2 uptake during the 30 s (VO2) and blood lactate accumulation (delta [L]s) were measured. Compared to normoxia, acute hypoxia at LA did not alter PP (8.0 +/- 1.1 vs 7.9 +/- 1.3 W.kg-1 BW) and MP (6.1 +/- 0.7 vs 6.1 +/- 1.1 W.kg-1 BW). Similarly, compared to chronic hypoxia, acute normoxia at HA did not modify these parameters (PP: 7.4 +/- 1.5 vs 7.3 +/- 1.8; MP: 5.4 +/- 1.2 vs 5.5 +/- 1.1; W.kg-1 BW). VO2 and delta [L]s were neither significantly changed by acute hypoxia at LA (520 +/- 50 vs 550 +/- 60 ml O2; 5.3 +/- 1.7 vs 4.8 +/- 1.7 mmol.l-1) nor by acute normoxia at HA (530 +/- 110 vs 500 +/- 90 ml O2; 3.4 +/- 1.3 vs 3.3 +/- 1.0 mmol.l-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Total lung capacity (TLC) and its components, including residual volume (RV) and vital capacity (VC), are described in a sample of 164 male and 143 female youths of Aymara ancestry (10.0-19.9 years) who were born and raised at high altitudes (> 2,500 m) and who were residing in La Paz, Bolivia (average altitude of about 3,600 m). The hypothesis was tested that the enhanced lung volumes of adult highlanders are attained during the period of growth and development. As found in adult male highlanders, TLC in young highlanders was significantly larger than in lowlanders of the same sex and body size, primarily as a result of increases in RV and secondarily through increases in VC. In addition, estimates of the magnitude of the effect of chronic hypobaric hypoxia on all of the measures of pulmonary function, including TLC, RV, and VC, were positively related to age. This finding suggests that growth and development at high altitude is associated with a constant increase in TLC and other measures of pulmonary function relative to those of lowlanders, a finding which is consistent with the expectations of the developmental adaptation hypothesis. However, although these relationships were statistically significant in males, they were not significant in females. Thus, although the magnitude of the estimated effects of chronic hypobaric hypoxia on TLC, RV, and VC were similar in males and females, the developmental pattern by which these enhanced volumes are achieved may differ between sexes.

SummaryMaximal aerobic power (V˙o2max) was assessed in seven male and one female middle- and long-distance recreational runners residing in La Paz, Bolivia (3600m). All runners were born and raised at high altitudes (>2500). Mean V˙o2max in the male runners was 60·8 ml/kg/min while V˙o2max in the female runner was 55·5 ml/kg/min. These values are higher than in any previously reported sample of either trained or untrained highaltitude natives. In addition, mean V˙o2max in the La Paz male runners and V˙o2max in the La Paz female runner were very similar to those found in comparable low-altitude samples of recreational athletes, suggesting that the cardiorespiratory systems of both normally active and highly active native Andean highlanders are capable of successfully responding to the stress of hypobaric hypoxia. This ability may have both developmental and genetic components.

The present study was performed to evaluate the effects of chronic inspiratory hypoxia and its combination with physical exercise on plasma erythropoietin concentration ([EPO]). Eight natives from the Bolivian Plateau were investigated at 3,600 m above sea level at rest as well as during and up to 48 h after exhaustive exercise (EE) and 60 min of submaximal (60%) cycle ergometer exercise (SE). Ten sea-level subjects were used as a control group for resting values. The mean resting plasma [EPO] of the high-altitude group (19.5 +/- 0.7 mU/ml) did not differ from that of the sea-level group (18.1 +/- 0.4 mU/ml) but was higher than would be expected from the relationship between [EPO] and hematocrit at sea level. Five hours after both types of exercise, [EPO] decreased by 2.1 +/- 0.8 (EE, P < 0.01) and 1.6 +/- 0.8 mU/ml (SE, P < 0.05); 48 h after SE, [EPO] increased by 2.6 +/- 0.9 mU/ml (P < 0.05). It is concluded that 1) high-altitude natives need relatively high [EPO] to maintain their high hematocrit and 2) exercise at low basal arterial PO2 does not directly increase plasma [EPO] in high-altitude residents but seems to exert suppressive effects.

In 7-15-yr-old children living in La Paz (Bolivia, altitude 3,700 m) (HA): 1) Maximal oxygen consumption (VO2max) varies from 35 to 45 ml.min-1.kg-1 and maximal heart rate from 188 to 194 beats.min-1. These values are lower than those of their counterparts at low altitude (LA) by 10-20% and 10-15 b.min-1, respectively. 2) The anaerobic metabolism is not affected by chronic hypoxia if the nutritional conditions and pubertal development of HA and LA boys are the same. When related to percent of VO2max, submaximal O2 debts are similar at HA and LA. After supramaximal exercise, maximal O2 debts (45.7 +/- 2.7 vs 45.9 +/- 3.8 ml.kg-1) and blood lactate concentrations (7.6 +/- 0.6 vs 6.5 +/- 0.6 mmol.l-1) are also the same at HA and LA. No differences are observed between the 2 altitudes in ventilatory (60 vs 56% VO2max) and lactate (60 vs 65% VO2max) thresholds. The altitude of La Paz does not alter the anaerobic performance of a force-velocity test (from 6 to 10 W.kg-1) between the ages of 7 to 15 years but reduces by 14-17% the mean anaerobic power developed during a 30-s Wingate test. This decrease could be linked to a lower participation of glycolysis and aerobic metabolism at HA during this test. 3) Poor socio-economic and nutritional conditions do not modify the aerobic performance of boys living in La Paz but lead to lower maximal anaerobic power (from -17% to -25%) when compared with HA boys from a high socio-economic background.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of inspiratory hypoxia on the erythropoietin (EPO) system decisively depend on the duration of the exposure to the hypoxic environment. Whereas a stay of some hours in a hypobaric chamber leads to markedly increased serum [EPO] (Eckardt et al. 1989), it could be demonstrated by Milledge and Cotes (1985) that members of a Himalaya expedition had, after a rapid increase in EPO values, presented decreasing EPO values during the second half of their altitude exposure. Furthermore, Winslow et al. (1989) showed low EPO concentrations in the blood of high-altitude natives from Nepal and Chile, which are similar to those of subjects living at sea level. The reasons for the adaptation of the EPO response to chronic hypoxia are not completely understood. It may only in part be attributed to other adaptive processes, e.g., increased hemoglobin concentration [Hb] or lower pH values.

The effects of high altitude (HA, 3,700 m) on performance during a force-velocity test (maximal anaerobic power, MAnP) and a 30-s Wingate test (mean power, P) were studied in boys 7-15 yr of age. Forty-seven children acclimatized to HA were compared with 101 living at low altitude (LA, 330 m). They had the same good nutritional status and the same level of physical activities [average 5.4 +/- 1.1 (SD) and 5.2 +/- 1.9 h/wk at HA and LA, respectively]. They performed the two tests using the same calibrated cycle ergometer. For the Wingate test, O2 uptake (VO2) during the 30 s and the peak of blood lactate concentration ([L]p) during the recovery were also measured. No difference in MAnP was observed between HA and LA. P, [L]p, and VO2 were lower at HA. This suggests that the altitude of 3,700 m did not affect the performance of the force-velocity test but reduced that of the Wingate test. This decrease in P was linked to a lower participation of glycolysis and aerobic metabolism. The latter is related to a reduced aerobic performance at HA. In addition, the slopes of the relationships between age and MAnP, P, and [L]p were the same at HA and LA, indicating that chronic hypoxia did not alter the development of the anaerobic metabolism during puberty.

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.

Comparisons with 14 normal, younger, male native residents of La Paz showed that 20 patients with Monge’s syndrome have significantly higher mean body surface areas, hemoglobin, resting tidal volumes

High-altitude natives residing at similar altitudes exhibit varying degrees of erythrocytosis, depending in part upon their geographical location1 – 3. A recent report by Winslow et al3 suggests that hematocrit and hemoglobin levels correlate with circulating erythropoietin levels in such individuals. These authors contend that individuals with elevated erythropoietin levels may be functionally anemic even though the hematocrit and hemoglobin values are elevated.

Studies of the distribution of pulmonary blood flow (Q) at the altitude of La Paz (3,650 m) were extended to the left upper (LUZ) and left lower lung zones (LLZ) from those previously reported for the

Simultaneous isotope dilution curves were recorded from the right upper (QRUZ) and right lower lung zones (QRLZ) by surface scanning in the sitting and recumbent positions in 15 normal high-altitude-born (HAD) males and in 1 HAD female as well as from 3 male newcomers, using 10 muCi of 131I-HSA as a bolus injection into the right ventricle. Similar information was also obtained at sea level from 5 normal males. The mean percent distribution of total pulmonary blood flow (Q) to RUZ and RLZ in the two body postures indicate (1) that in the vertical position RUZ in males receives about 17% of Q regardless of altitude and elevation in mean pulmonary artery pressure (MPAP) in HAD of 8.6 mm Hg above that extant at sea level; (2) recumbency at high altitude showed QRUZ also to be lower than at sea level; (3) elevation in MPAP at altitude has no significant effect on changing the sea-level distribution pattern of pulmonary blood flow.

In a previous study we showed that there were no differences in anaerobic metabolism between groups of 11-yr-old children living at high (3,700 m) and low (330 m) altitudes. The aim of this study is to investigate changes in this metabolism during pubertal development. We compare blood lactate concentration ([L]) after maximal bicycle exercise in 20 boys acclimatized to high altitude (HA, 12 yr old) and at low altitude in 14 boys (LA1, 12 yr old) and in 13 boys (LA2, 14 yr old). The subjects had the same level of physical fitness and the same nutritional and socioeconomic status. Pubertal development was identified by salivary testosterone concentration ([T]). Results (means ± SE) showed 1) at the age of 12 years, [L] and [T] in HA were significantly higher than in LA1 ([L] was 9.2 ± 0.5 vs. 6.8 ± 0.5 mmol/l, [T] was 233 ± 66 vs. 132 ± 30 pmol/l), 2) [L] and [T] in HA were statistically the same as in LA2, and 3) a linear relationship between [L] and [T] was significant (P less than 0.05) in all HA and LA subjects. This suggests that the higher [L] in 12-yr-old boys living at HA could result in an enhanced anaerobic metabolism linked to an earlier gonadal maturation evaluated by testosterone level.

The forced vital capacity (FVC), forced expiratory volume in one second (FEV), and ratio of FEV to FVC (%FEV) of 161 male and 158 female youths of European ancestry who were born at high altitudes and who were residing in La Paz, Bolivia (average altitude of 3,600 m) were examined and compared with those for lowland Europeans and highland Aymara Amerindians. FVC and FEV were significantly larger (p less than .001) in the La Paz Europeans than in two lowland control samples of European ancestry, with the relative differences between samples varying from small (1.5-4.1%) to moderate (7.7-11.9%). It could not be determined whether the enhanced lung volumes of the La Paz European children were acquired through an accelerated development of lung volumes relative to stature during adolescence, as is the case for Amerindian highlanders. After controlling for body and chest size, FVC and FEV were significantly smaller in the La Paz Europeans than in highland Aymara (p less than .001), suggesting that the lung volumes of the Aymara are influenced by factors other than simply growth and development at high altitude. Finally, as found in Amerindians, chest size is an important determinant of intra-individual variation in lung function among highland Europeans.

The physical growth of urban Aymara children residing in La Paz, Bolivia (3,600 m) is described and compared with Amerindian children residing at low and high altitudes and with low-altitude U.S. children. The sample consists of 227 males (10.6-19.7 yr) and 219 females (11.2-19.8 yr). The urban La Paz children were taller at all ages than rural high altitude Amerindian children but similar in stature to urban high altitude children from Peru. The variation in stature among the high altitude populations was considerable, amounting to average differences between the tallest and shortest samples of about 10 cm in males and 8 cm in females. In addition, stature in the two urban high altitude samples was similar to that of rural low-altitude Amerindians. This overlapping of the distributions of stature in high- and low-altitude populations could easily confound comparisons designed to determine the effects of hypoxia on physical growth. La Paz Aymara children had considerably smaller chest sizes relative to stature than high-altitude Quechua children. However, the available data indicates that relative chest sizes are similar in Aymara and Quechua adults, suggesting that the process by which large chests are achieved may differ between these Andean populations.