Journal of Applied Physiology
Vol. 83, No. 2, pp. 661-667, August 1997
ENVIRONMENT

Exercise performance of Tibetan and Han adolescents at altitudes of 3,417 and 4,300 m

Qiu-Hong Chen, Ri-Li Ge, Xiao-Zhen Wang, Hui-Xin Chen, Tian-Yi Wu, Toshio Kobayashi, and Kazuhiko Yoshimura

Qinghai High Altitude Medical Science Institute, Xining, Qinghai 810012, China; and Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto 390, Japan

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

FOOTNOTES

REFERENCES

ABSTRACT

Chen, Qiu-Hong, Ri-Li Ge, Xiao-Zhen Wang, Hui-Xin Chen, Tian-Yi Wu, Toshio Kobayashi, and Kazuhiko Yoshimura. Exercise performance of Tibetan and Han adolescents at altitudes of 3,417 and 4,300 m. J. Appl. Physiol. 83(2): 661-667, 1997.The difference was studied between O₂ transport in lifelong Tibetan adolescents and in newcomer Han adolescents acclimatized to high altitude. We measured minute ventilation, maximal O₂ uptake, maximal cardiac output, and arterial O₂ saturation during maximal exercise, using the incremental exercise technique, at altitudes of 3,417 and 4,300 m. The groups were well matched for age, height, and nutritional status. The Tibetans had been living at the altitudes for a longer period than the Hans (14.5 ± 0.2 vs. 7.8 ± 0.8 yr at 3,417 m, P < 0.01; and 14.7 ± 0.3 vs. 5.3 ± 0.7 yr at 4,300 m, P < 0.01, respectively). At rest, Tibetans had significantly greater vital capacity and maximal voluntary ventilation than the Hans at both altitudes. At maximal exercise, Tibetans compared with Hans had higher maximal O₂ uptake (42.2 ± 1.7 vs. 36.7 ± 1.2 ml · min¹ · kg¹ at 3,417 m, P < 0.01; and 36.8 ± 1.9 vs. 30.0 ± 1.4 ml · min¹ · kg¹ at 4,300 m, P < 0.01, respectively) and greater maximal cardiac output (12.8 ± 0.3 vs. 11.4 ± 0.2 l/min at 3,417 m, P < 0.01; 11.5 ± 0.5 vs. 10.0 ± 0.5 l/min at 4,300 m, P < 0.05, respectively). Although the differences in arterial O₂ saturation between Tibetans and Hans were not significant at rest and during mild exercise, the differences became greater with increases in exercise workload at both altitudes. We concluded that exposure to high altitude from birth to adolescence resulted in an efficient O₂ transport and a greater aerobic exercise performance that may reflect a successful adaptation to life at high altitude.

cardiac output; maximal oxygen consumption; ventilation; developmental adaptation; genetic adaptation

INTRODUCTION

MAXIMAL O₂ uptake (O_{2 max}), an integrated index of the overall functional capacity of the O₂ transport system, invariably decreases with altitude during both acute and chronic exposure to high altitude in lowland adults (31, 34). This is due to the reduction of ambient O₂ pressure at high altitude. Although comparative studies of O_{2 max} between high altitude natives and lowland residents at high-altitude have been done, the conclusions are controversial (10-13, 30). High-altitude adult natives in either Andean or Himalayan populations have higher exercise performance and maintain better arterial O₂ saturation (Sa_O2) during exercise compared with newcomers (17, 20, 30, 38). These characteristics, which are associated with more efficient pulmonary gas exchange (38) and better adaptation to high-altitude stress, are acquired through many generations of lifelong high-altitude exposure. The Tibetans are believed to have lived at high altitude longer than other high-altitude residents. The effects of high-altitude hypoxia on the physiological responses of Tibetan and Han adolescents to exercise have never been reported. Whether the pulmonary adaptations in humans are determined purely by environment or relate to genetic characteristics has long been under investigation (3, 10, 11, 14, 16, 22, 23). However, the age at which these adaptations to hypoxic environment occur in humans is unclear.

Therefore, the objectives of this study were to investigate the effects of age of onset and the effects of duration of high-altitude exposure during the developmental period on exercise performance and O_{2 max} of Tibetan and Han adolescent males at altitudes of both 3,417 and 4,300 m. This study may provide information for better understanding of the mechanism(s) responsible for the process of adaptation to high altitude.

METHODS

Subjects

Table  1.   Physical characteristics of subjects at rest 3,417 m 4,300 m Tibetan Han P Tibetan Han P n 26 28 21 14 Age, yr 14.5 ± 0.2  14.8 ± 0.2  NS 14.7 ± 0.3  14.8 ± 0.3  NS Residence, yr 14.5 ± 0.2  7.8 ± 0.8  <0.01 14.7 ± 0.3  5.3 ± 0.7  <0.01 Body wt, kg 45.6 ± 1.4  44.1 ± 1.5  NS 45.4 ± 1.7  46.9 ± 1.6  NS Ht, cm 160.7 ± 2.3  159.8 ± 1.6  NS 153.6 ± 1.8  157.1 ± 2.8  NS BSA, m2  1.41 ± 0.04  1.38 ± 0.02  NS 1.38 ± 0.03  1.40 ± 0.05  NS Hct, %  46.8 ± 0.9  48.5 ± 0.6  NS 48.7 ± 0.2  50.8 ± 1.1  NS VC, liters 3.39 ± 0.14  2.66 ± 0.14  <0.01 3.44 ± 0.17  2.58 ± 0.12  <0.01 FEV1, liters 3.01 ± 0.14  2.44 ± 0.13  <0.01 3.16 ± 0.16  2.61 ± 0.13  <0.05 FEV1, %  91.9 ± 1.0  92.8 ± 0.7  NS 91.0 ± 1.4  94.2 ± 1.1  NS MVV, l/min 92.7 ± 4.7  73.3 ± 4.1  <0.01 95.7 ± 4.7  78.5 ± 4.7  <0.01 VC/BW, ml/kg 75.9 ± 2.9  61.9 ± 3.4  <0.01 76.8 ± 3.5  55.5 ± 2.6  <0.01 MVV/BW, l · min1 · kg1 2.07 ± 0.09  1.69 ± 0.09  <0.01 2.13 ± 0.10  1.67 ± 0.08  <0.01  E, l/min BTPS 12.8 ± 0.6  11.5 ± 0.6  NS 11.3 ± 0.5  12.0 ± 0.6  NS  O2, l/min STPD 0.34 ± 0.02  0.30 ± 0.04  NS 0.30 ± 0.01  0.28 ± 0.01  NS  CO2, l/min STPD 0.29 ± 0.02  0.27 ± 0.03  NS 0.26 ± 0.01  0.24 ± 0.01  NS R 0.85 ± 0.01  0.89 ± 0.01  NS 0.87 ± 0.01  0.86 ± 0.01  NS HR, beats/min 83 ± 2  86 ± 3  NS 80 ± 2  82 ± 2  NS CO, l/min 4.9 ± 0.2  4.8 ± 0.2  NS 4.4 ± 0.2  4.3 ± 0.3  NS SaO2, %  89.7 ± 0.9  89.2 ± 1.1  NS 88.5 ± 0.8  87.2 ± 1.1  NS Values are means ± SE; n, no. of subjects; BSA, body surface area; Hct, hematocrit; VC, vital capacity; FEV1, forced expiratory volume in 1 s; MVV, maximal voluntary ventilation; BW, body weight; E, minute expiratory ventilation; O2, O2 uptake; CO2, CO2 production; R, respiratory quotient; HR, heart rate; CO, cardiac output; SaO2, arterial O2 saturation; NS, not significant.

Experimental Procedure

1

1

Statistical Analysis

RESULTS

The Tibetan and the Han subjects were similar in age, height, body weight, and body surface area. The Tibetan subjects have been living at high altitude for significantly longer periods than the Han subjects (Table 1). The ages of migration by the Han subjects to high altitude were 6.9 ± 0.8 yr (range, 0.4-13.5 yr) at 3,417 m and 9.4 ± 0.7 yr (range, 5.5-14.0 yr) at 4,300 m. No difference was found in the hematocrit values between the two groups.

At rest, there were no differences in E, O₂, CO₂, R, HR, CO, and Sa_O2 between the two groups at both altitudes. The values of VC, FEV₁, and MVV were significantly higher in the Tibetan subjects than those in the Han subjects (Table 1).

The maximal exercise values at altitudes of 3,417 and 4,300 m are shown in Table 2. Although the Tibetans tended to attain higher levels of maximal workload than the Hans at 3,417 m, there was no statistical difference between two groups. At 4,300 m, the Tibetans achieved significantly higher workload (P < 0.01) than the Hans. At maximal exercise, ventilation was higher in the Tibetans than in the Hans at 3,417 m, but it did not differ between two groups at 4,300 m (Table 2). No difference was found in R and maximal E (E_max)/O_{2 max} between the two groups at both altitudes. The Tibetan subjects had higher O_{2 max} than the Han subjects at both altitudes (Fig. 1). No difference was found in CO₂ between two groups at altitude of 3,417 m; however, the Tibetan subjects had higher values of CO₂ than the Hans at 4,300 m.

Table  2.   Ventilatory and hemodynamic characteristics during maximal exercise 3,417 m 4,300 m 3,417 vs. 4,300 m Tibetan Han P Tibetan Han P Tibetan P Han P n 26 28 21 14  E, l/min 62.3 ± 2.5  54.4 ± 1.8  <0.01 65.1 ± 3.2  57.1 ± 3.4  NS NS NS  O2, l/min 1.87 ± 0.08  1.61 ± 0.08  <0.05 1.63 ± 0.08  1.38 ± 0.07  <0.05 NS NS  O2, ml · min1 · kg1 42.2 ± 1.7  36.7 ± 1.2  <0.01 36.8 ± 1.9  30.0 ± 1.4  <0.01 <0.05 <0.01  CO2, l/min 1.88 ± 0.10  1.66 ± 0.06  NS 1.70 ± 0.08  1.42 ± 0.06  <0.01 NS <0.01 R 1.01 ± 0.03  1.05 ± 0.03  NS 1.05 ± 0.01  1.04 ± 0.01  NS NS NS  E/O 2, 33.6 ± 0.7  35.6 ± 1.0  NS 44.4 ± 1.7  46.1 ± 2.1  NS <0.01 <0.01 HR, beats/min 196 ± 2  196 ± 1  NS 195 ± 2  196 ± 3  NS NS NS SV, ml 64.8 ± 2.1  57.7 ± 1.4  <0.01 59.5 ± 2.5  51.1 ± 2.3  <0.05 NS <0.01 CO, l/min 12.8 ± 0.3  11.4 ± 0.2  <0.01 11.5 ± 0.5  10.0 ± 0.5  <0.05 <0.05 <0.01 SaO2, %  85.0 ± 0.8  80.5 ± 1.2  <0.01 82.2 ± 1.0  72.1 ± 2.1  <0.01 <0.05 <0.01 Workload, W 123.5 ± 4.7  112.5 ± 3.8  NS 116.9 ± 4.3  92.9 ± 5.1  <0.01 NS <0.01 Values are means ± SE; E/O2 , ventilation equivalent; SV, stroke volume.

The values of SV and CO in the Tibetan subjects were greater than those in the Han subjects at both altitudes (Fig. 2). The maximal CO (CO_max) showed a linear relationship with the O_{2 max} at both altitudes (Fig. 3).

Figure 4 shows the relationship between the values of O₂ at each workload and Sa_O2, including rest through maximal exercise for all groups. The O₂ increased with exercise in all groups. Although no differences in Sa_O2 between Tibetans and Hans were observed at rest and during mild exercise, the differences became greater with the increases in O₂ at both altitudes (Fig. 4). The levels of Sa_O2 at maximal exercise in the Han subjects were significantly lower than those in the Tibetans at both altitudes (Table 2).

DISCUSSION

Although the subjects in the present study were well-matched in age, body size, and nutritional condition, we observed that the values of VC, FEV₁, and MVV in the Tibetan subjects were significantly higher than those in the Han subjects. Frisancho (10) and Frisancho et al. (11) reported that the FVC of high-altitude natives, sea-level subjects, and lowland natives who acclimatized to high altitude during growth were dependent on the time of life when acclimatization takes place, because the lowland natives who acclimatized to high altitude attained the same values of FVC as the high-altitude natives. Frisancho et al. concluded that the enlarged lung volume of the highland natives is the result of changes occuring during growth and development. Thus the differences in VC, FEV₁, and MVV in our study may be primarily due to the age at which high-altitude exposure began, because the Tibetans had been living at high altitude since birth, whereas the Hans were born at sea level and immigrated to the high altitude.

The greater O_{2 max} observed in the Tibetan subjects at both altitudes may be associated with better performance at several steps of the O₂ transport system. Although we found trends of higher values of E_max in the Tibetan subjects at both altitudes, the ventilatory equivalent (E/O₂) was similar in both groups (Table 2). Therefore, the Tibetans attained a higher E_max due to an increased lung volume rather than hyperventilation (i.e., an increased alveolar ventilation per unit metabolic rate). Indeed, Grover et al. (15) demonstrated that the continuing increase in E was observed during maximal exercise at 3,100 m, while O_{2 max} remained at its maximal level, suggesting that pulmonary ventilation does not appear to limit O₂ at high altitude.

We did not estimate the alveolar-arterial O₂ difference. However, Wagner et al. (32) and West et al. (34) demonstrated that diffusion limitation of O₂ transport in the lungs became obvious during exercise at high altitude. Zhuang et al. (38) recently reported that Tibetans had a lower alveolar-arterial O₂ gradient coupled with higher Sa_O2 than Hans during heavy exer- cise, suggesting that Tibetans may have benefited from less diffusion limitation between alveolar gas and capillary blood (32) and better ventilation/perfusion matching during exercise. Remmers and Mithoefer (25) reported that permanent residents (Andean Indians) in La Paz, Bolivia, at high altitude (3,700 m) revealed increased values of pulmonary carbon monoxide diffusing capacity (DL_CO) compared with acclimatized lowlanders. DeGraff et al. (7) and Cerny et al. (5) demonstrated that Caucasian residents of Leadville, CO (3,100 m), who were either lifelong residents or migrants to Leadville as adolescents or adults, showed higher DL_CO than lowland subjects. Experimental animal studies by Burri and Weibel (4) and Bartlett and Remmers (2) demonstrated that young rats exposed to high altitude developed a larger pulmonary diffusing capacity or surface area than lowland controls, suggesting that rats raised at high altitude developed a larger pulmonary gas-exchange apparatus. Johnson et al. (19) also reported that lung volume at a given transpulmonary pressure and DL_CO were significantly greater in beagles raised at high altitude than in lowland controls. Because the pulmonary diffusing capacity is related in part to the alveolar surface area, the enhanced O_{2 max} of the Tibetan subjects in the present study, who have higher VC, is probably due to their having a greater alveolar surface area and an increased capillary volume. Indeed, we demonstrated that the values of CO_max showed linear relationships with the O_{2 max} at both altitudes (Fig. 3).

We have previously reported (12) that adult Tibetan natives at 4,700 m have higher exercise performance but lower O_{2 max} than do acclimatized adult Hans. This performance level is associated with higher anaerobic threshold values and lower blood lactate concentrations in the Tibetans. Previous observations by Zhuang et al. (37) demonstrated that increasing duration of high-altitude residence correlated with decreasing hypoxic ventilatory response. Lahiri et al. (22) reported that most children up to the age of 12 yr showed an increased hypoxic ventilatory response that was blunted with increasing age to a decreased response, and the blunting was completed by 22 yr of age independent of an individual's parentage and genetic background. Thus the disparity between the present results and the previous data (12) may be due to differences between adolescents and adults in physiological responses to high altitude.

The CO in this study was estimated by noninvasive technique, because an invasive method such as cardiac catheterization is difficult to use at high altitude, especially in children. Although the CO values obtained by the impedance method showed good correlation with those obtained by the Fick principle method (8), it should be understood that this method has some limitations, particularly with regard to measurements during exercise. However, because all data were collected by using the same method and because each test exhibited similar good reproducibility between runs, it is possible to discuss the differences between groups. However, we should be very careful about the validity of the absolute values.

The difference in the cardiac function between high- altitude natives and acclimatized lowlanders may be due to the difference in the myocardial contractility and/or pulmonary pressor response to both hypoxia and exercise. Reduction of CO is chiefly due to decrease in SV during exercise at high altitude by newcomers. This decrease in SV could be due to a depression of myocardial function due to lowered coronary arterial O₂ tension, reduced coronary blood flow (1), reduced plasma volume (36), and hypoxic pulmonary hypertension (16). However, Reeves et al. (24) demonstrated that the cardiac function was well preserved for a given O₂ in the normal volunteers at simulated high altitude, and O₂ breathing did not increase cardiac function, suggesting that high-altitude hypoxia causes little impairment of cardiac function, and that cardiac function may not limit O_{2 max} at high altitude. Our data demonstrated that the Tibetan subjects have higher values of SV coupled with higher Sa_O2 at maximal exercise than did the Hans. This result may be derived from either lower pulmonary arterial pressure (Ppa) (16) or higher myocardial contractility caused by relatively higher O₂ transport in the myocardium (30) or both.

Consistent with the observations made by others (28, 38), we noted that the Tibetans maintained significantly higher Sa_O2 values during maximal exercise at high altitude than did the Hans, suggesting that the Tibetans have higher diffusing capacity compared with the Hans. Schoene et al. (28) reported that high-altitude natives attained high levels of exercise with a ventilatory response to exercise that was comparable to or lower than that achieved by lowlanders who exercised at workloads comparable to highlanders with acute hypoxia. The lowlanders demonstrated a marked decrease in Sa_O2 during exercise. The maintenance of Sa_O2 during exercise that was observed in highlanders appeared to be attributed in large part to an increase in diffusing capacity. Johnson (18) also reported that the pulmonary diffusing capacity is important as a factor limiting the rate of O₂ delivery to tissues in normal persons during heavy exercise at high altitude. This evidence suggests that the diffusing capacity could be a decisive factor for O₂ transport during maximal exercise at high altitude. Thus our data indicate that, during the adolescent period, the Tibetan subjects have a greater capacity than do the Han subjects in their O₂ transport systems.

Our findings also indicate that the Tibetan subjects may have acclimatized more successfully to the high-altitude environment compared with the Han subjects. Two hypotheses have been proposed to explain the better adaptation to hypoxia. 1) High-altitude natives have adapted genetically to hypoxia through the many generations of high-altitude exposure (16, 23). 2) Adaptation to hypoxia is acquired through the process of growth and development (10, 11, 22). Groves et al. (16) reported that the resting mean Ppa and pulmonary vascular resistance (PVR) in five healthy young Tibetan adults at 3,658 m were within sea-level normal values, and the subjects revealed blunted hypoxic pulmonary vasoconstriction (HPV) and no reduction in Ppa and PVR in response to 100% O₂ inhalation. Durmowicz et al. (9) demonstrated that, compared with cattle living at high altitude, yaks (Bos grunniens) native to high altitudes showed smaller HPV response with less right ventricular hypertrophy; thinner-walled pulmonary arteries with less smooth muscle; and longer, wider, and rounder pulmonary artery endothelial cells. Sakai et al. (26) studied the differences in pulmonary hemodynamic characteristics between pikas (genus Ochotona), as high-altitude-adapted animals, and Wistar rats. They clearly demonstrated that significantly lower values of Ppa, PVR, and the ratio of right to left ventricular weight were observed in pikas than in rats at various altitudes of 4,460, 3,300, 2,300, and 610 m. Will et al. (35) and Weir et al. (33) demonstrated that offspring of cattle that were found to be either susceptible or resistant to the development of "brisket disease" retained their respective susceptible or resistant trait for at least two generations. These reports suggest that the differences in pulmonary vascular responses to high altitude between highland natives and lowlanders could be attributable to genetic adaptation.

Other evidence suggests that the adaptive responses in respiratory physiology and the attainment of the aerobic capacity at high altitude in highland native people are determined by environmental rather than genetic factors. Lahiri et al. (22) demonstrated that the ventilatory response to hypoxia and VC are similar in neonates and infants at sea level and at high altitude, and VC tends to increase in the postnatal period and continues to increase throughout the adolescent period. Frisancho (10) and Frisancho et al. (11) also reported that lowland natives who acclimatized to high altitude during growth attained the same values of FVC as the highland natives, and lowland natives who acclimatized to high altitudes as adults had significantly lower FVC than highland natives. These observations suggest that the increased lung volume of high-altitude natives is the result of adaptative changes acquired during growth and development. Previous studies in experimental animals (2, 4, 6, 19) that demonstrated that the growing animals raised at high altitude exhibited an augmented proliferation of alveolar units and surface area, as well as increased lung volume and diffusing capacity, also support this hypothesis.

The studies that support the hypothesis that pulmonary adaptative responses to high altitude are determined by environmental and/or developmental factors (2, 4, 6, 10, 11, 19, 22) seem to argue against the presumptions that are in accord with the genetic hypothesis implication (3, 9, 16, 26, 33, 35). It could be proposed, however, that the mechanisms responsible for the process of pulmonary adaptation to high-altitude environment may include both considerations. 1) Pulmonary gas-exchange functions, such as lung volume and diffusing capacity, may be more strongly influenced by environmental and developmental component. 2) Pulmonary vascular responsiveness, particularly an increased magnitude of HPV, may be primarily predisposed by genetic factors.

ACKNOWLEDGEMENTS

The authors appreciate the excellent secretarial assistance by Chieko Kamijo and Eiko Sato.

FOOTNOTES

Address for reprint requests: K. Yoshimura, Research Center on Aging and Adaptation, Shinshu Univ. School of Medicine, 3-1-1 Asahi, Matsumoto 390, Japan.

Received 15 August 1996; accepted in final form 26 March 1997.

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