Eur J Appl Physiol (1995) 71:543-548 © Springer-Verlag 1995

Wenzhong Niu • Youan Wu • Bo Li Ningrong Chen • Shizhong Song

Effects of long-term acclimatization in lowlanders migrating to high altitude: comparison with high altitude residents

Accepted: 18 April 1995

Abstract The physiological response to submaximal and maximal exercise was assessed in lowlanders and Tibetans at low (500 m above sea level) and high alti- tude-(HA, 3 680 m). The times spent at HA by the lowland migrators was 8 days (n = 60), 7 months (n = 60, same group), 15 months (n = 29) and 27 months (n = 29). After the 15-month stay at HA, the maximal oxygen uptake (l?O2m~x) and maximal heart rate of the lowland migrators almost reached those of the HA native residents (Tibetans, n = 57), but their total work capacity and the gross efficiency (r/) of mech- anical work remained lower than those of the Tibetans. The rate of l)'O2m,x achieved at 90 W by the Tibetans was lower than that of the lowland migrators. It was concluded that, at HA, the lowlanders regained much of the aerobic capacity which they had lost initially. However, they did not attain the same gross mechan- ical efficiency as the Tibetans, who seemed to be at an advantage in respect of work at HA.

Key words High altitude • Hypoxia • Natives • Exercise • Oxygen uptake

Introduction

It has been found that exposure to high altitude (HA) lowers physical capacity and greatly reduces exercise endurance in humans (Reeves 1987). By contrast, it has been shown that chronic hypobaric hypoxia has little effect on peak muscle power relying on anaerobic lactate energy (Kayser et al. 1993; Niu et al. 1994). The ,"

W. Niu (I:~). Y. Wu • B. Li . N. Chen Institute of Basic Medical Science, no. 134, Tianxianqiao Qianjie, Chengdu, Sichuan, 610061, P.R. China

S. Song Hygiene Division of Shannan Medical Association, Shannan, Tibet, 856000, P.R. China

Tibetans have lived at HA for thousands of years and appear to be well adapted to that environment. It has been found that lowland natives migrating to HA do not seem to attain a similar level of acclimatization to hypoxia and their physical capacity at HA remains lower, compared to HA residents (Dua and Gupta 1980). The exact causes of the differences in physical capacity at HA between lowland migrators and HA residents are not completely understood. To gain more insight into this, the physiological response to submaxi- mal and maximal exercise of lowlanders, lowland mi- grators to HA, and HA native Tibetans was assessed and compared. Exposure times to HA of the lowland migrators was 8 days, 7 months, 15 months and 27 months, respectively. The hypothesis tested was that part of the differences between migrators to HA and natives of HA results from differences in the relative rate (in %) of maximal oxygen uptake (l)O2ma~) during submaximal exercise at 90 W and in gross efficiency (r/).

Methods

Subjects

A group of 60 subjects was chosen at random among 600 healthy young men in Meishan county (500 m above sea level). They had been born and brought up at low altitude (less than 2 000 m, low- landers). Upon completion of the experimental protocol at Meishan, they were taken to HA (Lhasa 3 680 m). On the 8th day (migrator group 1) and at 7 months (migrator group 2), the experimental protocol was repeated. At the same location, another 58 young male migrators having lived at HA for 15 (n = 29) or 27 months (n = 29), also underwent the experimental protocol (migrator groups 3 and 4). As the HA control group, 57 native healthy young Tibetans were recruited. They had been born and brought up at HA between 3 000 m and 4 500 m.

Experimental protocol

The measurement of stature, body mass (using a scale, ZT-120, Wuxi Scale Plant, P.R. China) and vital capacity (VC, by a vital capacity

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meter, FHL-I, Shenyang Educational Instrument Factory, P.R. China) following "Methods and criteria of comprehensive assess- ment on physical capacity of Chinese students (1989)". The subjects exercised on an electromagnetic braked cycle ergometer (EGM-II, Yueyang Electric Instrument Factory, P.R. China). The ergometer was calibrated before the assessment of each group. After resting for 20 to 30 min, the subjects started to exercise from 0 W at 60 rpm and 30 W were added every 3 min. After 3 min at 90 W, 30 W were added every 2 min until exhaustion was reached. The criteria for exhaus- tion were: 1. The subject's heart rate (HR) was higher than 180 beats' min 1; 2. They could not maintain the imposed pedalling rate of

60 rpm; 3. The subject showed symptoms of extreme fatigue.

If a subject met two or three of the above criteria, he was con- sidered exhausted and the exercise was stopped. The HR was re- corded by electrocardiography during the last 5 s at each grade. At the end of each exercise intensity, the expired gas of the subjects was coIlected using Douglas bags and pulmonary ventilation (I)E, atmospheric temperature and pressure saturated) was measured using a dry gas meter (TM-2, Chengdu Gas Company, P.R. China). The expired gas was analysed for its oxygen and carbon dioxide contents with O2 and CO2 meter (CYES-II, Jiading Xuelian Instru- ment Plant, P.R. China) and l/E (standard temperature and pressure, dry, STPD), I)~ (body temperature pressure saturated, BTPS), oxygen uptake (902, STPD) and CO2 production (I/COa, STPD) were calculated. The gas analyser was calibrated using samples of known composition. Work done was calculated as work rate (WR) x t. The work a subject had performed on the ergometer at all grades was added up and defined as total work capacity (TWC). The performance of a subject at 90 W during the cycling exercise was used to assess his submaximal exercise performance. The ratio of 1/O2 (90 W) to gO2max was used to define a relative rate of l?O2max.

The gross mechanical efficiency 0~) was calculated following the following equation

W R x t gross t/(%) = . x 100% (1)

VO2 x 20.9

where WR is in kilograms per metre per minute, 20.9 is the energy equivalent of 1 1 of 02, assuming a respiratory quotient of 0.98, t is time (in seconds).

The oxygen pulse (O2,v) was defined as I/O2/HR.

Statistics

The group means of the various parameters measured were compared by ANOVA. In the event of a significant F-value differ- ences between pairs were tested with the post-hoc Student- Newman-Keuls test. Results were considered significant at P less than 0.05.

Results

Anthropometric data

The subjects were young and their anthropometric data were similar, with the exception of body mass. The Tibetans had slightly, but significantly, lower body mass than the lowlanders and the migrators, with the exception of migrator group 3 (Table 1).

Maximal exercise performance

In Table 2 it is shown that all the subjects completed the 90 W ergometer exercise. Not surprisingly, the low- landers attained higher maximal exercise intensities than the HA residents. More Tibetans attained exercise intensities between 120 W and 180 W compared to the migrators (see Table 2).

Table 3 shows that, compared with the lowlanders, TWC of both the migrator groups and the Tibetans was lower (P < 0.01) and their maximal minute ventila- tion (l/E . . . . . BTPS) was higher (P < 0.05-0.01). After the lowlanders had migrated to HA, all of the indexes tested initially decreased then subsequently increased slowly as time went on, with the exception of I?E,ma x.

Table 2 Ergometer exericse results. W R Work rate. For other def- initions see Table 1

WR Subjects (n) (w)

Lowlanders Tibetans MG 1 M G 2 M G 3 M G 4

0 60 30 60 60 60 90 60

120 60 150 60 180 60 210 48

240 14 270 1 300 1

57 58 54 29 29 57 58 54 29 29 57 58 54 29 29 57 58 54 29 29

52 36 44 25 25 34 6 13 6 9

6 2 1 1

Table 1 Anthropometric data. VC vital capacity, MG 1 migrator group 1 the migrators who had lived at high altitude (HA) for 8 days, MG 2 migrator group 2 - the migrators who had lived at HA for 7 months, MG 3 migrator group 3 - the migrators who had lived at HA for 15 months, MG 4 migrator group 4 - the migrators who had lived at HA for 27 months.

Altitude Group n Age Height Body mass VC (m) (years) (cm) (kg) (1)

Mean SD Mean SD Mean SD Mean SD 500 Lowlanders 60 18.7 0.9 168.8 4.2 62.0 5.4** 4.00 0.44

Tibetans 57 19.0 1.0 167.8 4.9 56.0 6.1 4.01 0.63 MG 1 58 18.7 0.9 168.8 4.2 61.0 5.2** 3.90 0.62

3680 M G 2 54 19.3 0.8 168.9 4.9 60.8 5.9** 3.88 0.48 MG 3 29 20.8 0.8 170.0 5.4 58.1 4.8 3.83 0.49 M G 4 29 22.5 0.9 169.0 5.0 60.0 6.7** 3.86 0.45

** P < 0.01 Compared with the Tibetans

Table 3 The performance of maximal exercise at high altitude. T W C Total work capacities, HRma~ maximal heatrate, 1202max maximal oxygen uptake, l?Emax maximal minute ventilation, O2,Pm~x maximal oxygen pulse, BTPS Body temperature pressure, saturated, for other definitions see Table 1

Altitude Group n HRmax rO2max

(beats. min- 1) (1" rain i)

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(ml. kg- 1. min- 1)

Mean SD Mean SD Mean SD 500m Lowlanders 60 191 8.1 2.673 0.374 43.9 5.58

Tibetans 57 185 16.4" 2.264 0.435** 41.5 8.60 MG1 58 180 8.9 **a 2 . 0 5 6 0.251 **b 33.8 3.26 **b

3 680m MG2 54 183 9.9** 2.249 0.302** 37.1 4.08 **b MG3 29 187 8.0* 2.334 0.248** 40.4 4.85** MG4 29 188 9.8 2.320 0.251"* 39.7 4.15'*

Altitude Group n TWC II E .... (BTPS) (kgf.m.kg 1) (1.min 1)

O2,Pmax (ml" kg- 1. beats- 1)

500m Lowlanders 60 179 .2 31.17 115.2 14.46

Tibetans 57 98.1 20.39** 121.8 15.76" MG1 58 65.0 18.29 **b 127.6 19.41"*

3 680m MG2 54 76.9 16.09 **b 130 .2 8.78** MG3 29 80.5 13.70 **a 123.8 15.71" MG4 29 81.0 14.68 **a 126.5 14.34"

0.23 0.023

0.22 0.028 0.19 0.026 **b 0.20 0.021 **b 0.21 0.022 **a 0.21 0.028 **a

*P < 0.05 Compared with the lowlanders, **P < 0.01, ap < 0.05 compared Tibetans, bp < 0.01

with the

Table 4 The performance of submaximal exercise (90 W) at high altitude. 1702 Oxygen uptake, gO2max maximal oxygen uptake, HR heart rate, O2p oxygen pulse, VCO2 carbon- dioxide production. For other definitions see Table 1

Altitude Group n VO 2 (ro2/DO2max) HR (1. rain- 1) (%) (beats" min- 1)

Mean SD Mean SD 500m Lowlanders 60 1 .474 0.220 49.65 145 14.8

Tibetans 57 1 .727 0.240** 74.22* 166 18.0"* MG1 58 1 .818 0.263 **b 88.16'* 177 9.3 **b

3 680m MG2 54 1 .915 0.143 **b 84.90** 180 12.4 **b MG3 29 1 .944 0.136 **b 82.92** 183 9.1 **u MG4 29 1 .997 0.155 **u 83.88** 183 13.1 **b

Altitude Group n O2,p Gross ~/ 1)O2 (ml" kg- 1. beats- 1) (%) (1" min 1)

500m Lowlanders 60 0 .156 0.023 17.53 1.404 0.202

Tibetans 57 0.184 0.030** 14.96 2.051 0.258* MG1 58 0 .171 0.027 **b 13.19 2.206 0.253 **b

3680m MG2 54 0 .170 0.016 **u 13.49 2.282 0.259 **b MG3 29 0 .177 0.015"* 13.29 2.065 0.253** MG4 29 0 .176 0.018"* 12.93 2.046 0.228**

* P < 0.05 Compared with the lowlanders, ** P < 0.01; bp < 0.01 compared with the Tibetans

T h e va lues of a b s o l u t e gO2max as well as specific gO2max for b o d y m a s s of the m i g r a t o r g r o u p 1 were sma l l e r t h a n those of the o t h e r m i g r a t o r g roups . T h e l)'O2m~x a n d HRma x of the m i g r a t o r s g r o u p s were no l o n g e r a n y di f ferent to the va lues o b s e r v e d in the T ibe t ans , af ter 15 m o n t h s of H A exposu re , b u t the i r m a x i m a l o x y g e n pu l se (O2,Pmax = l)O2max/HRma×) a n d T W C were stil l s ign i f i can t ly l o w e r t h a n those of the T i b e t a n s ( P < 0.05-0.01) .

S u b m a x i m a l exerc ise p e r f o r m a n c e

T a b l e 4 shows t ha t H R (90 W), 1202 (90 W) a n d O2p (90 W) i nc r ea sed wi th t ime spen t a t HA. T h e l o n g e r the exposu re , the h ighe r the va lues for these p a r a m e t e r s , i n d i c a t i n g c o n t i n u o u s a c c l i m a t i z a t i o n of the h u m a n b o d y to h y p o x i a . T h e l?O2max ach i eved b y the m i g r a - to r s r e m a i n e d h ighe r t h a n t h a t of the T i b e t a n s ( P < 0.05), even af ter t hey h a d l ived at H A for 27

70- months. From Eq. 1, it follows that for equivalent work rates, at higher values of gross i/, less oxygen is con- sumed. The gross r/ of the lowlanders was the highest among the six groups, whereas that of the Tibetans was higher than that of the migrators. The calculated O2p (90 W) of the Tibetans was higher than that of the migrators. The migrator groups 1 and 2 had higher values of I?CO2 than the other groups, whereas the lowlanders' value of I/CO2 was the lowest among all six groups.

Relationship between WR and I202

In Fig. 1 the relationship is shown between WR and 1/O2 of all groups. The slopes of the six lines were similar, indicating that the energy cost of muscle con- traction is the same (equal net mechanical efficiency), whereas the intercepts were different, reflecting the dif- ferences in the gross t/.

40

60 o" .>

.>~ 50

30.

3.0

546

0 60 120 180 240 300

Work rate (W)

Fig. 2 Relationship between minute ventilation (body temperature and pressure, saturated)/oxygen uptake (l) E (BTPS)/1202) and work rate. [] [] Lowlander group, © © Tibetan group, A - - A migrator group 1, A - - - A migrator group 2, • - - - • migrator 3, I 1 - - - I I migrator 4. For details of different groups see Table 1

Relationship between WR and l/z (BTPS)/I?O2

In Fig. 2, it can be seen that the pattern of change in the proportion of t7"O2 to 17~ of the lowlanders was differ- ent from that of the HA residents. At low altitude, with increasing power output, 1)'O2 and I?E increased, but the increase of 1/O2 was b!gger than that of l?~ and the relationship between VE/V02 and WR was a concave curve. At HA the relationship between l)z/l)02 and WR of the migrators was initially shifted to higher values, however with time it decreased but not to the

f 2.5

i c _ 2.0 E

v

0 ~ 1.5 .>

1.0

0.5

0 60 120 180 240 300

Work rate (W)

Fig. 1 02 uptake (l)O2m,x) against work rate for six groups. [] --F1 Lowlander group, © - - - © Tibetan group, & - - - & migrator group 1,/~- 2x migrator group 2, • - - • migrator 3, • - - I I migrator 4. For details of different groups see Table 1

low altitude values. The Tibetans had similar values compared to the acclimatized lowlanders, except for the higher WR when the Tibetans seemed to ventilate more for a given 1202.

Discussion

The gO2max is a physiological index of human aerobic capacity. It is useful in assessing cardiopulmonary func- tion and physical performance capacity. It has been reported that acute exposure to HA in lowlanders de- creases l)O2max (Paterson et al. 1987; Faulkner et al. 1968). In the present stud.y (Table 3) both migrat- ors and Tibetans had lower VO2max and TWC than the lowlanders, a finding confirming the reported effects of hypoxia on aerobic work capacity. However, with time, the migrators' acclimatization allowed them to regain an important fraction of the gOzmax lost. There was a reduction of 23.0% of the migrators' l?O2max after 8 days, but only of 15.5% after 7 months and only about 8.0% after 15 months. At 15 months the value of their 1202m~x was not significantly different from that of the Tibetans. Acclimatization is a process that may apparently take up to at least 15 months to complete, after arrival at HA. In the acute phase at HA, the symptoms and signs of acute mountain sickness (AMS) will normally disappear after about a week. Compared with the recovery of AMS, the restoration of physical work capacity at HA appears far slower. Table 3 shows the gradual restoration of aerobic capacity of the mi- grators at HA, eventually attaining similar levels com- pared to the Tibetans. One would therefore expect the migrators also to attain the same work capacity as the Tibetans. However, this was not the case and their TWC and the percentage of migrators who finished

547

cycling on the ergometer at 120 to 180 W was much less than that of the Tibetans. We found that 9Ozmax is not therefore reliable in assessing the physical work capa- city of a subject at HA.

Because endurance exercise is performed at levels below maximal exercise intensity, the exercise level is related to the percentage of VO2max in addition to the 1702max itself. For equivalent 902m,x, the lower the percentage of 9Ozma~ used at 90 W, the higher the work capacity (Exercise physiological Editorial Group 1984). The percentage of 9Ozmax while exercising at 90 W of the Tibetans was lower than that of the migra- tors, which may in part explain the difference in the physical work capacity between the Tibetans and the migrators.

It was also observed that for exercise at a given power output at HA, more 902 was needed than at low altitude. This finding contrasts with the findings of Pugh et al. (1963) and West et al. (1983). Those authors have reported the same 902 for a given WR at HA as at sea level. Lower 902 for a given power output has also been reported by Hochachka et al. (1990) in An- dean Indians (Quechuas) and explained by an increased mechanical efficiency compared to lowlanders. How- ever, this would change the slope of the line 9 0 2 compared to WR and as can be seen in Fig. 1 the slopes are not significantly different, whereas the intercepts do differ. Our findings are at variance with recent findings ofGe et al. (1994) who have found a lower A VOz/AWR in Tibetans compared to migrators. We have no ex- planation for this difference but we feel that further evidence should be sought before the paradigm of a fixed net mechanical efficiency in humans at low and high altitude can be discarded.

To take up on equal volume of O2 at HA more ventilation is required than at low altitude. More venti- lation requires a higher rate of work of the respiratory muscles and consequently more 02 is consumed by the respiratory muscles. However, the difference in ventila- tory rates between low altitude and high altitude can- not explain all differences between 902 in these condi- tions and there are probably other factors which also play a role. Maybe a difference in the resting metabolic rate could be another factor.

The energy cost, i.e. A VOz/AWR , of exercise at HA is the same as at low altitude. The strategy of the human body to supply the muscles with the same volume of O.2 in the acute phase are increased cardiac output and Vz and at a later stage higher haemoglobin (Hb) concentration. Indeed, VE and 9Em,x at HA were higher than at low altitude, comfirming previous results (Zhang and Fan 1990). During exercise at 90 W, the 9~ and 1202 of the HA residents were higher than those of the lowlanders. Thus, it seems reasonable to postu- late that part of the excess O2 taken up by HA residents was consumed by the more intense contraction of the respiratory muscles. Because the air and alveolar par- tial pressures of 02 (PO2) at HA are lower than those

at the low altitude, the alveolar-arterial PO 2 difference in the lungs is also lower. As far as the blood gas barrier is concerned, only a small increase of the 02 diffusion occurs at HA and the main strategy for HA residents is to increase 9E. But, limited by the anatomy of the respiratory tract, the 12 E cannot be increased indefinite- ly and 902m,x at HA cannot reach the level of 902max at low altitude. We did not measure Hb concentration or arterial Hb saturation, but it seems evident that our migrators would have had higher levels of Hb and Hb saturation after acclimatization, both features helping to restore mass oxygen transport to the periphery.

It may also be speculated that with time the oxygen diffusion in the lungs may have improved somewhat, also helping to improve 902. Perhaps this is another pos- sible explanation of the Tibetans' greater 9Ozmax than that of migrators, especially in the acute phase at HA. In any case a very long time is necessary for lowlanders exposed to HA to improve 902.

It was found that gross r/of HA residents was lower than that of the lowlanders. The main reason for this is the higher 902 at rest. This maybe due to the higher basal metabolic rate at altitude in the migrators. In addition, some increased 902 may have come from the higher l)" E at HA.

Physical work capacity increases as the rate of 902max increases. We found that the ratio of 902 (90 W): 902max of the migrators improved as their stay at HA grew longer. After 15 months the rate appeared stable, but it was still worse than that of the Tibetans, which may explain in part the difference of the physical work capacity between the migrators and Tibetans.

The O2p reflects the capacity of the oxygen transport system in the blood at each heart beat and is an index enabling evaluation of the heart function. The O2,Pmax and Ozp (90 W) values of the Tibetans were signifi- cantly higher than those of the migrators (P < 0.05-0.01). When doing submaximal exercise, the Tibetans' HR was lower than that of the migrators. This would suggest that the Tibetans have a higher cardiac output or a greater oxygen extraction rate in the periphery than that of the migrators.

It has been reported that HRmax of subjects exposed to HA decreases (Paterson et al. 1987; Li 1990). But some studies have reported that there were not any significant differences between lowlanders' HRmax and that of people exposed to HA (4 000 m above sea level; Stenberg et al. 1966; Buskirk et al. 1967). In out study during the acute phase (8 days), HRmax of the migrators had decreased markedly from 191 beats'rain -1 to 180 beats'rain -1 (5.7%). With time the migrators' HRm,x increased again. After 27 months at HA, their HRm~x was 188 beats 'rain-1, which was slightly higher than that of the Tibetans (185 beats" rain-1) and not signifi- cantly different from that of the lowlanders. It is pro- posed that the differences to previous reports resulted from different exposure times at HA and differences in levels of acclimatization.

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There are many papers which claim that the body mass decreased after lowlanders arrived at HA, but apart from a small 2% initial decrease our study failed to confirm this. It is thought that the decrease of the body mass comes from loss of body water, loss of appetite and changes of living conditions. Once AMS has subsided, hypoxia itself has little effects on body mass. After acclimatization, mass loss can be regained.

In conclusion, it would appear that lowlanders mi- grating to HA initially lose a large fraction of their aerobic capacity as well as decrease their gross t/during physical work. With time both indexes improve con- siderably, but not to the same level of altitude natives like the Tibetans. The latter seem indeed to be better adapted for work at altitude since their gross t/is better than that of acclimatized lowlanders. It remains to be proved whether this is an inborn feature or the result of a life long exposure to hypobaric hypoxia.

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