Effect of developmental and ancestral high-altitude exposure on VO(2)peak of Andean and European/North American natives

Peak oxygen consumption (VO(2)peak) 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 VO(2)peak 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 VO(2)peak 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 VO(2)peak 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 VO(2)peak, 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.     

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.     

Effect of altitude on the lung function of high altitude residents of European ancestry

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.     

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.     

Pulmonary gas exchange and acid-base state at 5,260 m in high-altitude Bolivians and acclimatized lowlanders.

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% O2 only L showed a significant increase. During exercise in air, arterial PCO2 was 8 Torr lower in L than in N (P < 0.001), yet PO2 was the same such that, at maximal O2 uptake, alveolar-arterial PO2 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 PCO2 responses to hyperoxia); 3) during exercise, greater pulmonary diffusing capacity than in L, allowing maintenance of arterial PO2 despite 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.     

Effects of birthplace and individual genetic admixture on lung volume and exercise phenotypes of Peruvian Quechua

Forced vital capacity (FVC) and maximal exercise response were measured in two populations of Peruvian males (age, 18-35 years) at 4,338 m who differed by the environment in which they were born and raised, i.e., high altitude (Cerro de Pasco, Peru, BHA, n = 39) and sea level (Lima, Peru, BSL, n = 32). BSL subjects were transported from sea level to 4,338 m, and were evaluated within 24 hr of exposure to hypobaric hypoxia. Individual admixture level (ADMIX, % Spanish ancestry) was estimated for each subject, using 22 ancestry-informative genetic markers and also by skin reflectance measurement (MEL). Birthplace accounted for the approximately 10% larger FVC (P < 0.001), approximately 15% higher maximal oxygen consumption (VO(2)max, ml.min(-1).kg(-1)) (P < 0.001), and approximately 5% higher arterial oxygen saturation during exercise (SpO(2)) (P < 0.001) of BHA subjects. ADMIX was low in both study groups, averaging 9.5 +/- 2.6% and 2.1 +/- 0.3% in BSL and BHA subjects, respectively. Mean underarm MEL was significantly higher in the BSL group (P < 0.001), despite higher ADMIX. ADMIX was not associated with any study phenotype, but study power was not sufficient to evaluate hypotheses of genetic adaptation via the ADMIX variable. MEL and FVC were positively correlated in the BHA (P = 0.035) but not BSL (P = 0.335) subjects. However, MEL and ADMIX were not correlated across the entire study sample (P = 0.282). In summary, results from this study emphasize the importance of developmental adaptation to high altitude. While the MEL-FVC correlation may reflect genetic adaptation to high altitude, study results suggest that alternate (environmental) explanations be considered.     

Increased exercise SaO2 independent of ventilatory acclimatization at 4,300 m

Arterial O2 saturation (Sao2) decreases in hypoxia in the transition from rest to moderate exercise, but it is unknown whether other several weeks at high altitude SaO2 in submaximal exercise follows the same time course and pattern as that of ventilatory acclimatization in resting subjects. Ventilatory acclimatization is essentially complete after approximately 1 wk at 4,300 m, such that improvement in submaximal exercise SaO2 would then require other mechanisms. On days 2, 8, and 22 on Pikes Peak (4,300 m), 6 male subjects performed prolonged steady-state cycle exercise at 79% maximal O2 uptake (VO2 max). Resting SaO2 rose from day 1 (78.4 +/- 1.6%) to day 8 (87.5 +/- 1.4%) and then did not increase further by day 20 (86.4 +/- 0.6%). During exercise, SaO2 values (mean of 5-, 15-, and 30-min measurements) were 72.7% (day 2), 78.6% (day 8), and 82.3% (day 22), meaning that all of the increase in resting SaO2 occurred from day 1 to day 8, but exercise SaO2 increased from day 2 to day 8 (5.9%) and then increased further from day 8 to day 22 (3.7%). On day 22, the exercise SaO2 was higher than on day 8 despite an unchanged ventilation and O2 consumption. The increased exercise SaO2 was accompanied by decreased CO2 production. The mechanisms responsible for the increased exercise SaO2 require further investigation.     

Metabolic and work efficiencies during exercise in Andean natives

Maximum O2 and CO2 fluxes during exercise were less perturbed by hypoxia in Quechua natives from the Andes than in lowlanders. In exploring how this was achieved, we found that, for a given work rate, Quechua highlanders at 4,200 m accumulated substantially less lactate than lowlanders at sea level normoxia (approximately 5-7 vs. 10-14 mM) despite hypobaric hypoxia. This phenomenon, known as the lactate paradox, was entirely refractory to normoxia-hypoxia transitions. In lowlanders, the lactate paradox is an acclimation; however, in Quechuas, the lactate paradox is an expression of metabolic organization that did not deacclimate, at least over the 6-wk period of our study. Thus it was concluded that this metabolic organization is a developmentally or genetically fixed characteristic selected because of the efficiency advantage of aerobic metabolism (high ATP yield per mol of substrate metabolized) compared with anaerobic glycolysis. Measurements of respiratory quotient indicated preferential use of carbohydrate as fuel for muscle work, which is also advantageous in hypoxia because it maximizes the yield of ATP per mol of O2 consumed. Finally, minimizing the cost of muscle work was also reflected in energetic efficiency as classically defined (power output per metabolic power input); this was evident at all work rates but was most pronounced at submaximal work rates (efficiency approximately 1.5 times higher than in lowlander athletes). Because plots of power output vs. metabolic power input did not extrapolate to the origin, it was concluded 1) that exercise in both groups sustained a significant ATP expenditure not convertible to mechanical work but 2) that this expenditure was downregulated in Andean natives by thus far unexplained mechanisms.     

Pulmonary gas exchange at maximal exercise in Danish lowlanders during 8 wk of acclimatization to 4,100 m and in high-altitude Aymara natives

We aimed to test effects of altitude acclimatization on pulmonary gas exchange at maximal exercise. Six lowlanders were studied at sea level, in acute hypoxia (AH), and after 2 and 8 wk of acclimatization to 4,100 m (2W and 8W) and compared with Aymara high-altitude natives residing at this altitude. As expected, alveolar Po2 was reduced during AH but increased gradually during acclimatization (61 +/- 0.7, 69 +/- 0.9, and 72 +/- 1.4 mmHg in AH, 2W, and 8W, respectively), reaching values significantly higher than in Aymaras (67 +/- 0.6 mmHg). Arterial Po2 (PaO2) also decreased during exercise in AH but increased significantly with acclimatization (51 +/- 1.1, 58 +/- 1.7, and 62 +/- 1.6 mmHg in AH, 2W, and 8W, respectively). PaO2 in lowlanders reached levels that were not different from those in high-altitude natives (66 +/- 1.2 mmHg). Arterial O2 saturation (SaO2) decreased during maximum exercise compared with rest in AH and after 2W and 8W: 73.3 +/- 1.4, 76.9 +/- 1.7, and 79.3 +/- 1.6%, respectively. After 8W, SaO2 in lowlanders was not significantly different from that in Aymaras (82.7 +/- 1%). An improved pulmonary gas exchange with acclimatization was evidenced by a decreased ventilatory equivalent of O2 after 8W: 59 +/- 4, 58 +/- 4, and 52 +/- 4 l x min x l O2(-1), respectively. The ventilatory equivalent of O2 reached levels not different from that of Aymaras (51 +/- 3 l x min x l O2(-1)). However, increases in exercise alveolar Po2 and PaO2 with acclimatization had no net effect on alveolar-arterial Po2 difference in lowlanders (10 +/- 1.3, 11 +/- 1.5, and 10 +/- 2.1 mmHg in AH, 2W, and 8W, respectively), which remained significantly higher than in Aymaras (1 +/- 1.4 mmHg). In conclusion, lowlanders substantially improve pulmonary gas exchange with acclimatization, but even acclimatization for 8 wk is insufficient to achieve levels reached by high-altitude natives.     

Percent of oxygen saturation of arterial hemoglobin among Bolivian Aymara at 3,900–4,000 m

A range of variation in percent of oxygen saturation of arterial hemoglobin (SaO₂) among healthy individuals at a given high altitude indicates differences in physiological hypoxemia despite uniform ambient hypoxic stress. In populations native to the Tibetan plateau, a significant portion of the variance is attributable to additive genetic factors, and there is a major gene influencing SaO₂. To determine whether there is genetic variance in other high-altitude populations, we designed a study to test the hypothesis that additive genetic factors contribute to phenotypic variation in SaO₂ among Aymara natives of the Andean plateau, a population geographically distant from the Tibetan plateau and with a long, separate history of high-altitude residence. The average SaO₂ of 381 Aymara at 3,900–4,000 m was 92 ± 0.15% (SEM) with a range of 84–99%. The average was 2.6% higher than the average SaO₂ of a sample of Tibetans at 3,800–4,065 m measured with the same techniques. Quantitative genetic analyses of the Aymara sample detected no significant variance attributable to genetic factors. The presence of genetic variance in SaO₂ in the Tibetan sample and its absence in the Aymara sample indicate there is potential for natural selection on this trait in the Tibetan but not the Aymara population. Am J Phys Anthropol 108:41–51, 1999. © 1999 Wiley-Liss, Inc.     

Effects of human pregnancy and aerobic conditioning on alveolar gas exchange during exercise

This study examined the effects of aerobic conditioning during the second and third trimesters of human pregnancy on ventilatory responses to graded cycling. Previously sedentary pregnant women were assigned randomly to an exercise group (n = 14) or a nonexercising control group (n = 14). Data were collected at 15-17 weeks, 25-27 weeks and 34-36 weeks of pregnancy. Testing involved 20 W.min-1 increases in work rate to a heart rate of 170 beats.min-1 and (or) volitional fatigue. Breath-by-breath ventilatory and alveolar gas exchange measurements were compared at rest, a standard submaximal .VO2 and peak exercise. Within both groups, resting .V(E), .V(A), and V(T)/T(I) increased significantly with advancing gestation. Peak work rate, O2 pulse (.VO2/HR), .V(E), .V(A) respiratory rate, V(T)/T(I), .VO2, .VCO2, and the ventilatory threshold (T(vent)) were increased after physical conditioning. Chronic maternal exercise has no significant effect on pregnancy-induced changes in ventilation and (or) alveolar gas exchange at rest or during standard submaximal exercise. Training-induced increases in T(vent) and peak oxygen pulse support the efficacy of prenatal fitness programs to improve maternal work capacity.     

Developmental components of resting ventilation among high- and low-altitude Andean children and adults

This paper evaluates the age-associated changes of resting ventilation of 115 high- and low-altitude Aymara subjects, of whom 61 were from the rural Aymara village of Ventilla situated at an average altitude of 4,200 m and 54 from the rural village of Caranavi situated at an average altitude of 900 m. Comparison of the age patterns of resting ventilation suggests the following conclusions: 1) the resting ventilation (ml/kg/min) of high-altitude natives is markedly higher than that of low-altitude natives; 2) the age decline of ventilation is similar in both lowlanders and highlanders, but the starting point and therefore the age decline are much higher at high altitude; 3) the resting ventilation that characterizes high-altitude Andean natives is developmentally expressed in the same manner as it is at low altitude; and 4) the resting ventilation (ml/kg/min) of Aymara high-altitude natives is between 40–80% lower than that of Tibetans. Am J Phys Anthropol 109:295–301, 1999. © 1999 Wiley-Liss, Inc.     

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives

Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.     

Exercise VE and physical performance at altitude are not affected by menstrual cycle phase.

We hypothesized that progesterone-mediated ventilatory stimulation during the midluteal phase of the menstrual cycle would increase exercise minute ventilation (VE; l/min) at sea level (SL) and with acute altitude (AA) exposure but would only increase arterial O2 saturation (SaO2, %) with AA exposure. We further hypothesized that an increased exercise SaO2 with AA exposure would enhance O2 transport and improve both peak O2 uptake (VO2 peak; ml x kg-1 x min-1) and submaximal exercise time to exhaustion (Exh; min) in the midluteal phase. Eight female lowlanders [33 +/- 3 (mean +/- SD) yr, 58 +/- 6 kg] completed a VO2 peak and Exh test at 70% of their altitude-specific VO2 peak at SL and with AA exposure to 4,300 m in a hypobaric chamber (446 mmHg) in their early follicular and midluteal phases. Progesterone levels increased (P < 0.05) approximately 20-fold from the early follicular to midluteal phase at SL and AA. Peak VE (101 +/- 17) and submaximal VE (55 +/- 9) were not affected by cycle phase or altitude. Submaximal SaO2 did not differ between cycle phases at SL, but it was 3% higher during the midluteal phase with AA exposure. Neither VO2 peak nor Exh time was affected by cycle phase at SL or AA. We conclude that, despite significantly increased progesterone levels in the midluteal phase, exercise VE is not increased at SL or AA. Moreover, neither maximal nor submaximal exercise performance is affected by menstrual cycle phase at SL or AA.     

Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara

Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800–4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3–4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations. Am J Phys Anthropol 106:385–400, 1998. © 1998 Wiley-Liss, Inc.     

Altitude acclimatization attenuates plasma ammonia accumulation during submaximal exercise

This study examined the effects of acclimatization to 4,300 m altitude on changes in plasma ammonia concentrations with 30 min of submaximal [75% maximal O2 uptake (VO2max)] cycle exercise. Human test subjects were divided into a sedentary (n = 6) and active group (n = 5). Maximal uptake (VO2max) was determined at sea level and at high altitude (HA; 4,300 m) after acute (t less than 24 h) and chronic (t = 13 days) exposure. The VO2max of both groups decreased 32% with acute HA when compared with sea level. In the sedentary group, VO2max decreased an additional 16% after 13 days of continuous residence at 4,300 m, whereas VO2max in the active group showed no further change. In both sedentary and active subjects, plasma ammonia concentrations were increased (P less than 0.05) over resting levels immediately after submaximal exercise at sea level as well as during acute HA exposure. With chronic HA exposure, the active group showed no increase in plasma ammonia immediately after submaximal exercise, whereas the postexercise ammonia in the sedentary group was elevated but to a lesser extent than at sea level or with acute HA exposure. Thus postexercise plasma ammonia concentration was decreased with altitude acclimatization when compared with ammonia concentrations following exercise performed at the same relative intensity at sea level or acute HA. This decrease in ammonia accumulation may contribute to enhanced endurance performance and altered substrate utilization with exercise following acclimatization to altitude.     

Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia.

Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude. The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no significant effects on normoxic exercise, and 2) sildenafil would improve cardiac output, arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained men performed one practice and three experimental trials at sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test consisted of a set-work-rate portion (55% work capacity: 1 h SL, 30 min HA) followed immediately by a time trial (10 km SL, 6 km HA). Double-blinded capsules (placebo, 50, or 100 mg) were taken 1 h before exercise in a randomly counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% oxygen) 1 h before exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), cardiac output, and SaO2 during set-work-rate exercise. Sildenafil lowered 6-km time-trial time by 15% (P<0.05). SaO2 was also higher during the time trial (P<0.05) in response to sildenafil, despite higher work rates. Post hoc analyses revealed two subject groups, sildenafil responders and nonresponders, who improved time-trial performance by 39% (P<0.05) and 1.0%, respectively. No dose-response effects were observed. During cycling exercise in acute hypoxia, sildenafil can greatly improve cardiovascular function, SaO2, and performance for certain individuals.     

Iron deficiency anemia and steady-state work performance at high altitude

Thirty-seven young adult male highland residents at 3,600-4,100 m in La Paz, Bolivia, performed short-duration cycle ergometry at 60, 80, and 100% of maximal voluntary O2 consumption (VO2max). Three groups of subjects representing the high-altitude population mean hemoglobin (Hb), the 10th percentile Hb, and below the 1st percentile were examined to test the hypothesis that the relationship of exercise performance to Hb concentration is similar to those relationships established at low altitude. Anemic individuals (n = 8) had 23% lower voluntary VO2max and 28% lower maximal work loads compared with controls (n = 17) or marginally anemic subjects (n = 12) although the relationship of VO2 to work load was similar. Anemic individuals maintained significantly higher arterial O2 partial pressures and Hb saturations during heavy exercise (90 +/- 0.5 vs. 85 +/- 0.6%) in conjunction with a greater heart rate up to maximal effort. A significantly decreased erythrocyte 2,3-diphosphoglycerate (2,3-DPG)-to-Hb molar ratio (0.70 +/- 0.04 vs. 1.12 +/- 0.06), suggestive of a left-shifted dissociation curve in anemics, is in contrast to the expected right-shifted curve. Moderate anemics were similar to controls. Anemic individuals did not differ in arterial lactate concentration from controls at absolute work loads; anemics had significantly lower arterial lactate concentrations at maximal effort than controls with no differences in the work load-to-lactate relationship. In conclusion, O2 transport during exercise at high altitude seems unaffected by the Hb concentrations as low as the 10th percentile of the population mean.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neonatal Variables,Altitude of Residence and Aymara Ancestry in Northern Chile

Studies performed in the Andean plateau, one of the highest inhabited areas in the world, have reported that reduced availability of oxygen is associated to fetal growth retardation and lower birth weight, which are established predictors of morbidity and mortality during the first year of life. To test this hypothesis, perinatal variables of neonates born at the Juan Noé Hospital of Arica, Chile, were analyzed in relation to altitude of residence and Aymara ancestry of their mothers. The study population comprised the offspring of 5,295 mothers born between February 2004 and August 2010. Information included birth weight, height, head circumference, gestational age, altitude of residence and socioeconomic status, and was obtained from medical records. Mother´s ancestry was assessed based on surnames which were linked to percentages of Aymara admixture estimates relying on 40 selected ancestry informative markers. After correcting for the effect of multicollinearity among predictor variables, neonates born to mothers with an increased component of Aymara ancestry showed significantly higher birth weight and height at sea level, a marginally significant (p-value 0.06) decrease of birth weight and a significant decrease of height with altitude in comparison with the offspring of mothers with low Aymara ancestry. Since observed tendencies are suggestive of a possible genetic adaptation to hypoxia of the Chilean Aymara, we discuss briefly preliminary evidence related to fetal oxygen transport, particularly polymorphisms in the promoters of the HBG1 and HBG2 genes that are modulators of HbF synthesis, obtained in this ethnic group.     

Developmental and genetic components explain enhanced pulmonary volumes of female peruvian Quechua

High altitude natives have enlarged vital capacities and residual volumes (RV). Because pulmonary volumes are an indication of functionally relevant traits, such as diffusion capacity, the understanding of the factors (genetic/developmental) that influence lung volumes provides insight into the adaptive responses of highlanders. In order to test for the effect of growth and development at high altitude on lung volumes, we obtained forced vital capacities (FVC), RV, and total lung capacities (TLC) for a sample of 65 Peruvian females of mostly Quechua origins (18-34 years) who were sub-divided into two well-matched groups: 1) sea-level born and raised females (BSL, n = 34) from Lima, Peru (150 m), and 2) high-altitude born and raised females (BHA, n = 31) from Cerro de Pasco, Peru (4,338 m). To determine Quechua origins, Native American ancestry proportion (NAAP) for each individual was assessed using a panel of 70 ancestry informative markers. NAAP was similar between groups (BSL = 91.71%; BHA = 89.93%; P = 0.240), and the analysis confirmed predominantly Quechua origins. After adjusting for body size and NAAP, BHA females had significantly higher FVC (3.79 ± 0.06 l; P < 0.001), RV (0.98 ± 0.03 l; P < 0.001) and TLC (4.80 ± 0.07 l; P < 0.001) compared to BSL females (FVC = 3.33 ± 0.05 l; RV = 0.69 ± 0.03 l; TLC = 4.02 ± 0.06 l). NAAP was not associated with FVC (P = 0.352) or TLC (P = 0.506). However, NAAP was positively associated with RV (P = 0.004). In summary, results indicate that developmental exposure to high altitude in females constitutes an important factor for all lung volumes, whereas both genetic and developmental factors seem to be important for RV.