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3 Copenhagen Muscle Research Centre, Copenhagen, Denmark 2200; 2 Instituto Boliviano de Biologia de Altura, Bolivia; and 1 Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California 92093
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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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.
hypoxia; ventilation; acid-base balance; diffusing capacity
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE REMARKABLE ABILITIES of high-altitude natives to perform work at altitude are well known (15), and much research has been carried out to understand the physiological basis of this phenomenon. Considerable attention has been focused on the lungs, and several studies point to differences in lung structure and function between high-altitude natives and lowlanders of Tibet (23), South America (15), and even the United States (6). Some of the differences appear to be inherited adaptations consequent to generations of living at altitude. Others may result from individual lifelong or at least long-term high-altitude residence, whereas others may occur over the short term of days to weeks. Principal observations are that lung volumes are greater than predicted by sea-level tables (15, 23) and that diffusing capacity is also elevated (4-6, 9, 15). Reduced ventilatory response to hypoxia is often (6, 15) but not always (22) seen, resulting in arterial PCO2 values that are higher in high-altitude natives than in lowlanders. Despite this, arterial oxygenation is defended during exercise by a smaller alveolar-arterial PO2 difference [(A-a)PO2] in natives compared with lowlanders, such that arterial O2 saturation is similar between groups (6) or even higher in natives (23). These findings have mostly been obtained at or below 4,000 m.
During a recent expedition to Mt. Chacaltaya (altitude 5,260 m) near La Paz, Bolivia, we took the opportunity to further explore differences in pulmonary function between South American high-altitude natives and lowlanders. This expedition was focused primarily on circulatory and skeletal muscle changes with acclimatization, and this required arterial blood sampling at rest and during exercise. Thus, whereas pulmonary function was not a primary target of the expedition, the gas-exchange and acid-base differences seen in the lowlanders compared with natives were substantial, prompting their description in the present report. What this study offered beyond those described above was a side-by-side comparison of lowlanders and Andean natives using identical methods and with direct arterial blood sampling not available in Schoene et al.'s work (15) in subjects of similar population ancestry. An unusual additional aspect of the present study was that the lowlanders had acclimatized for 9 wk at the chosen altitude before measurements. Most acclimatization studies have not allowed such a long period at a single altitude but have followed subjects as they inexorably continued to ascend, preventing attainment of steady-state conditions at any point. Moreover, the studies of Dempsey et al. (6), Zhuang et al. (23), and Schoene et al. (15) were all carried out at substantially lower altitudes (3,100, 3,658, and 3,900 m, respectively) than the present effort, which took place at 5,260 m. In the present study, measurements were made both at rest and during exercise and addressed the following questions: 1) Does 9 wk at this constant high altitude permit complete pH normalization (i.e., restoration of arterial pH to near 7.40) in lowlanders? 2) Does acute hypoxia in natives (who were necessarily transported on the day of the study from La Paz, altitude 3,600-4,100 m, to 5,260 m) produce a substantial additional stimulus to breathing at rest or during exercise, and a measurable reduction in exercise capacity as would occur for lowlanders moving between these altitudes? 3) Is arterial oxygenation during exercise still defended in natives at 5,260 m as appears to be the case at lower altitudes, and, if so, are the physiological mechanisms similar to those described above in prior studies [higher diffusing capacity and lower (A-a)PO2]? 4) Is arterial acid-base regulation similar in natives and acclimatized lowlanders?
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects.
This study used nine lowlanders from Denmark and seven Bolivian natives
of mixed European and Amerindian population ancestry, lifetime
residents of La Paz at between 3,600 and 4,100 m. All provided informed
consent to protocols approved by both Danish and Bolivian ethical
committees (Copenhagen-Fredericksberg Ethical Review Committee and
Comité de Etica del Colegio Médico de La Paz).
Anthropometric and key additional physiological attributes are given in
Table 1. All 16 subjects were healthy,
habitually active, and nonsmokers. The Danes were physically active
college students with an interest in outdoor recreation, whereas the
Bolivians indulged in a variety of regular social activities including
soccer. Only one Bolivian was a trained athlete (marathon runner).
There were small differences in age (Bolivians 3 yr older,
P = 0.05) and height (Bolivians 12 cm shorter,
P = 0.01), but weight and body mass index were not
significantly different. Both hemoglobin concentration and hemoglobin
PO2 at 50% saturation of hemoglobin (P50) were similar in the two groups (Table 1) as
well. Note from Table 1 that maximal cycling power output (that
is, highest power sustainable for the 5 min required for stabilization
and data collection) and associated O2 uptake
(
O2) when breathing ambient air at 5,260 m were also similar between groups.
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Subject preparation. The protocols were designed to simultaneously address several questions, many of which were well beyond those pertaining to pulmonary function, and thus required several catheters whose purposes are unrelated to the present report. Under local anesthesia and with sterile technique, catheters were placed in a femoral vein (94-030-2.5F TD probe, Edwards Edslab, Baxter, Irvine, CA) and artery (18-gauge Hydrocath, Ohmeda, Swindon, UK) to enable both blood sampling and measurements of femoral venous blood flow by thermodilution (1). A peripheral venous catheter was placed in an antecubital vein in the lowlanders, to be used for indocyanine green dye injection for cardiac output measurements. Cardiac output was also measured in the high-altitude natives, but with the use of an acetylene uptake method (2) to avoid additional catheters and blood sampling unacceptable to the subjects.
Subjects were then seated on a cycle ergometer (Monark 824E, Varberg, Sweden) and fitted with a mouthpiece and nose clip in standard fashion to enable measurements of ventilation,O2, and CO2 production
(CO2) from expired gas (using
ParvoMedics True Max 2400, Consentius Technologies, UT). An
electrocardiogram monitor was attached with standard leads to record
heart rate and oversee rhythm.
Protocol. Both lowlanders and high-altitude natives undertook identical protocols as follows. After resting measurements, a submaximal work rate averaging 120 W was selected, and subjects pedaled at this power output for 10 min, with duplicate measurements made in the final 5 min. After a 10-min rest, subjects again cycled at 120 W for 2 min, after which work rate was rapidly raised to the previously determined individual peak rate known to be sustainable for 5 min. During the final 2 min of this 5-min period, duplicate measurements were again obtained. With subjects still pedaling, a higher work rate was imposed if subjects indicated ability to continue, and measurements were repeated within 2 min. When each subject could increment work rate no further, the inspired gas was switched from ambient air [barometric pressure = 408 Torr; inspiratory PO2 (PIO2) = 75 Torr] to ~55% O2 (PIO2 = 195-200 Torr) while the subject continued to pedal. After 2 min, another set of measurements was taken, and work rate was further incremented individually if tolerated to attain a new peak power output. A final set of measurements was then obtained under these conditions.
It should be noted that the above was actually a subset of the entire day's protocol. Those elements that pertained to questions other than lung-related issues are not described here. These include submaximal and maximal exercise runs using single-leg knee extensor effort and also cycle exercise after parasympathetic nervous system blockade (reported elsewhere, Ref. 3). The knee extensor runs were done before those described for the present study and were separated from the present cycle exercise by an hour of rest, but the parasympathetic blockade experiments were always done after the present study had been completed.Measurements.
Other than O2,
CO2, and ventilation, the principal data
were obtained from arterial blood samples and consisted of
PO2, PCO2, and pH
(Radiometer ABL5); saturation and hemoglobin concentration (Radiometer
OSM3); and plasma lactate levels (ABL5). All values of
PO2, PCO2, and pH were
corrected to blood temperature measured by the femoral venous catheter
thermistor. Cardiac output was measured in lowlanders by indocyanine
green dye dilution with injection in a peripheral (antecubital) vein
and femoral arterial sampling (3). In natives, a
noninvasive method for measuring cardiac output was chosen to minimize
catheter placements and blood loss. We used the acetylene uptake method
(2) and employed the SensorMedics
O2 max system (SensorMedics, Yorba
Linda, CA) to measure acetylene (and an insoluble reference gas,
methane) concentrations at the mouth. This system also measures
ventilation and O2 and CO2 concentrations and
so provided all of the input data required for calculation of cardiac
output as explained in Barker et al.'s paper (2). Without
any equipment to measure acetylene solubility, we assumed for all
subjects an average blood:gas partition coefficient of 0.8 on the basis
of Barkers' results and an estimate from Jibelian et al.
(10) of the contribution of the higher than sea-level
hemoglobin concentration.
Calculations.
Oxygen-diffusing capacity of the lungs
(DLO2) was not directly measured at rest
or during exercise. However, a value for
DLO2 could be calculated from the measured
blood-gas data by use of a numerical forward-integration algorithm
(19) as follows. First, by using the measured pulmonary
O2, cardiac output, and arterial O2 concentrations, mixed venous O2 levels were
computed for each subject. Similar calculations were performed for
CO2. Alveolar PO2 was also
determined for each subject by using the alveolar gas equation and
taking alveolar PCO2 to be equal to arterial PCO2. Between these venous and alveolar values
for PO2 and PCO2, a
value of DLO2 was found (by using the
numerical integration procedure in an iterative manner) that predicted
the measured arterial PO2 and
PCO2 for each subject. The key assumption, made for both subject groups, was that all of the
(A-a)PO2 found during exercise at 5,260 m was
due to diffusion limitation and none was caused by
ventilation-perfusion inequality. The diffusing capacity was therefore
calculated by assuming a homogeneous lung and, as a result, is a
conservative lowest estimate. This assumption is seen in
DISCUSSION.
Analysis of data. The principal objective of this study was to compare several elements of exercise performance between high-altitude natives and acclimatized lowlanders. This was done by two-way ANOVA (subjects × exercise levels, the latter by repeated measures) followed by unpaired t-tests comparing subject groups at any exercise level when ANOVA indicated significant group effects. Data in figures and tables are given as means ± SE because the major interest is in mean differences between the two subject groups.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Resting gas exchange.
Lowlanders hyperventilated compared with natives. Figure
1 shows resting arterial
PO2, arterial PCO2, and
(A-a)PO2 in both groups.
PO2 was 8 Torr higher (50.0 ± 1.1 vs.
42.1 ± 0.7, P < 0.001) and
PCO2 9 Torr lower (21.1 ± 0.9 vs.
30.0 ± 0.3, P < 0.001) in lowlanders. However,
in both groups, (A-a)PO2 was similar and not
different from zero.
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5.6 vs. 3.5 meq/l respectively, P < 0.001). Resting arterial blood lactate levels were similar (1.5 and 1.4 mmol/l, P not significant). The lowlanders showed greater
perturbation of acid-base balance than the natives. It is remarkable
that in the natives, despite rapid ascent from 3,600-4,100 to
5,260 m over 2 h and an arterial O2 saturation of
77%, arterial pH was 7.43, hardly different from a normal pH of 7.40 or from values of resting arterial pH of 7.41 reported previously in
such natives at 3,600 m (17).
Ventilatory response to exercise.
Figure 2A shows that
O2 consumption at rest, submaximal exercise, and maximal
exercise while breathing ambient air at 5,260 m was essentially
identical in the two groups, allowing a comparison that is not
encumbered by questions of relative vs. absolute work rates nor by
differences in efficiency of O2 utilization. Figure 2B shows that lowlanders continued to mount a greater
ventilatory response than natives throughout exercise. At maximal
O2
(O2 max), minute ventilation was 163 l/min in the lowlanders vs. 131 l/min in the natives, a difference of
24%, P = 0.05. Not surprisingly, arterial
PCO2 remained lower in the lowlanders
throughout exercise as shown in Fig. 2C. At
O2 max, arterial
PCO2 was 7.4 Torr lower in the lowlanders (19.3 vs. 26.7, P < 0.001). Arterial PCO2 fell slightly from rest to exercise in
both groups (by 2 Torr in lowlanders and 3 Torr in natives,
P not significant).
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O2 max occurred in the face of
identical arterial PO2 [45.6 (lowlanders) and 46.0 Torr (natives)] and O2 saturation [72.1 (lowlanders)
and 72.3% (natives)], an arterial pH that was higher in the
lowlanders (7.37 vs. 7.33, P = 0.04), and an arterial
blood lactate concentration that was lower in the lowlanders (8.7 vs.
11.5 mmol/l, P = 0.04).
Comparing arterial PCO2 values during peak
exercise in air and (at the same power output) in 55% O2
provides additional insight into the ventilatory responsiveness to
hypoxia. Recall that, during air breathing, both maximal cycling power
output and arterial PO2 were similar in the two
groups. In the natives, arterial PCO2 rose
6.4% from 26.7 ± 1.0 to 28.4 ± 0.8 Torr, P = 0.02. In the lowlanders, PCO2 rose 22.8%
from 19.3 ± 0.8 to 23.7 ± 0.8 Torr, P < 0.001. The relative increase in PCO2 (and
therefore fall in alveolar ventilation) was thus 3.6-fold greater in
lowlanders than in natives when hypoxia was eliminated.
Arterial oxygenation and diffusing capacity during exercise.
With note taken of a similar cardiac output response to exercise (Fig.
3A), important to diffusion
equilibration, arterial PO2 during exercise was
not different between groups (Fig. 3B). This contrasts with
the higher PO2 in lowlanders at rest and
occurred despite the substantial differences in ventilation shown in
Fig. 2. Arterial O2 saturation followed arterial
PO2 (Fig. 3C), resulting in similar
values for arterial O2 concentration (not shown).
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Acid-base balance at rest and during exercise.
During maximal exercise, arterial pH fell from resting levels by
similar amounts in the two groups (7.48 to 7.37 in the lowlanders, a
difference of 0.11; 7.43 to 7.33 in the natives, a difference of 0.10).
Although arterial PCO2 values also fell by
similar amounts (2 and 3 Torr, respectively), there was a significant
difference in the arterial blood lactate concentrations: 8.7 ± 0.8 mmol/l in lowlanders and 11.5 ± 1.0 mmol/l in natives,
P = 0.04. Despite the lower blood lactate levels,
calculated base deficit was not smaller in the lowlanders. In fact,
base deficit was 12.0 ± 0.5 meq/l compared with 10.7 ± 0.7 in the natives. Figure 4 brings out these
differences in the relationship between base deficit and lactate levels
for the two groups. The scatter about the regression lines comes mostly
from differences between subjects in each group, given that individual
regressions all had correlation coefficients of 
0.8. A comparison of
the slopes and intercepts of the base deficit-lactate
relationship revealed that both the slope and intercept were
higher in the lowlanders (P < 0.001 each). In
particular, the slope was 20% higher in the lowlanders (0.97 ± 0.02 meq/mmol compared with 0.81 ± 0.03 in the natives), implying
less ability to buffer lactic acid during exercise, despite the
similarity in hemoglobin concentrations (Table 1).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The discussion corresponds to the four questions laid out in the introduction.
Rate of acclimatization in lowlanders at altitude. This study shows that, even after 9 wk at an altitude of 5,260 m, resting arterial pH is still alkaline (7.48), despite considerable renal bicarbonate excretion. These results contrast with those of Dempsey et al. (6), in which resting arterial pH was 7.42 for both sojourners and natives despite the latter having acclimatized for less time (4-45 days). However, this was at 3,100 m, substantially lower than in Bolivia. That arterial pH eventually normalizes at 5,260 m is suggested by the present native data. Their pH was 7.43 despite having ascended from La Paz (3,600-4,000 m, PIO2 of 95 Torr) to Chacaltaya (5,260 m, PIO2 of 75 Torr) in just 2 h and thus having been acutely exposed to significantly greater hypoxia than at their altitude of residence. The data of Vincent et al. (17) further support this conclusion: Arterial pH at La Paz was 7.41 and PCO2 was 31.3 Torr in natives breathing air at rest, barely different from our data at 5,260 m.
Zhuang et al. (23) showed that, at 3,658 m, high-altitude natives in Tibet also have a resting arterial pH of 7.40 and PCO2 of 30 Torr. They additionally assessed lowlanders who had been at 3,658 m for 1-2 yr and found pH to be 7.45, with arterial PCO2 at 28 Torr. Why were the lowlanders in both the present study and that of Zhuang hyperventilating to maintain pH at 7.45-7.48 after 9 wk to 2 yr at altitude? Acute hyperventilation associated with catheterization or the mouthpiece is a possibility but seems unlikely. Our lowlanders were young Danish students used to mouthpieces, catheters, and research studies, whereas for the natives this was a completely new experience, especially catheter placement, blood sampling, breathing on a mouthpiece, and being subjected to additional acute hypoxia. If anything, acute hyperventilation would have been expected in the natives, the opposite of what was observed. Moreover, Zhuang et al. (22) found that arterial saturation was unaffected by presence of a mouthpiece. A second possibility is that the classical Rahn and Otis (13) line depicting alveolar PO2 and PCO2 in acclimatized subjects does not represent complete acclimatization, which produces even greater ventilation with more time at altitude. Plotting the lowlander data on the Rahn and Otis diagram (Fig. 5) indicates that our subjects had an alveolar PO2 ~5 Torr higher and PCO2 4 Torr lower than expected.
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Possible influence on natives of rapid ascent from La Paz to Chacaltaya. Because our equipment could not be duplicated in La Paz nor readily moved between Chacaltaya and La Paz, the natives were studied at Chacaltaya (5,260 m) on arrival after a 2-h drive from La Paz (3,600-4,100 m). We therefore anticipated acute hyperventilation because PIO2 was 20 Torr lower than in La Paz. However, despite a resting arterial PO2 of 42 Torr (saturation 77%), PCO2 was 30 Torr and pH 7.43. Vincent et al.'s (17) La Paz data in similar resting subjects showed that arterial PO2 was 56 Torr (saturation estimated at about 90%), PCO2 was 31.3 Torr, and pH was 7.41. Thus, despite the large drop in saturation, there was evidence of very little increase in ventilation.
Vincent et al.'s (17) subjects fall right on the Rahn and Otis (13) line for acclimatized subjects (at 3,600 m) shown in Fig. 5 of the present paper. Rahn and Otis further showed how acute hypoxia affects alveolar PO2 and PCO2 in lowland subjects already acclimatized to various altitudes. From Fig. 5 of their paper, one estimates that La Paz natives taken acutely to 5,260 m would have had an alveolar PO2 of 45-46 Torr and PCO2 of 27-28 Torr, whereas our subjects displayed values of 42 and 30 Torr, respectively. Furthermore, because arterial saturation during constant-load exercise in each group was raised from 73 to 99% by breathing 55% O2, the natives increased arterial PCO2 by only 6.4% (whereas lowlanders increased PCO2 by 22.8%). These findings are compatible with the work of Schoene et al. (15), who showed that hypoxic ventilatory drive in high-altitude natives was blunted. The native responses are all the more astonishing given the low O2 saturation during exercise (Fig. 3) and the usual carotid body sensitivity to such hypoxemia (20). It was feared that the acute ascent not only would represent a major ventilatory stimulus, but would also compromise exercise capacity. The outcome, however, suggests otherwise. Thus maximal cycling power output was not significantly affected: 234 ± 6 W several days earlier in La Paz, compared with 217 ± 5 W at Chacaltaya. The lack of significant decrease in exercise capacity with acute ascent from 3,600-4,100 m to 5,260 m is consistent with (but more dramatic than) the findings of Favier et al. (7), who in similar subjects found only a minor (8%) decrease inO2 max at La Paz (3,600 m) between
31.4% O2, equivalent to sea-level air, and ambient air.
This insensitivity of O2 max to
PIO2 suggests that muscle metabolic
capacity in natives has been downregulated over time in response to
reduced O2 availability.
Pulmonary gas exchange during exercise. This study extends to 5,260 m the work of both Dempsey (6) at 3,100 m in North American high-altitude natives and Zhuang (23) at 3,658 m in Tibetan high-altitude natives. As in their work, a lower (A-a)PO2 preserves arterial PO2 and saturation at values seen in acclimatized lowlanders at the same work rate, despite the natives' higher arterial PCO2.
Because theoretical and experimental work shows that at altitude most of the (A-a)PO2 is due to alveolar-capillary diffusion limitation (18, 21), the likely basis of the lower (A-a)PO2 in high-altitude natives is higher diffusing capacity associated with larger lungs, as previously suggested (15, 23). Piiper and Scheid (11, 12) have shown that the degree of diffusion limitation depends on the ratio DLO2/(
· 
T),
where DLO2 is the O2 diffusing
capacity of the lungs, is the slope of the O2
dissociation curve, and T is cardiac output. In the
present study, and T (Fig. 3) were similar
between natives and lowlanders. The depends on hemoglobin
concentration (similar, Table 1), in vivo P50 (similar at
31.7 and 32.0 Torr), and arterial and venous
PO2 and saturation (arterial similar, Fig. 3;
venous similar by calculation from O2,
cardiac output, and arterial values, Figs. 2 and 3). Thus it is the
40% higher calculated DLO2 in natives that underlies the smaller (A-a)PO2 and
preserves arterial PO2.
Cardiac output was measured by dye dilution in lowlanders and by
acetylene uptake in natives. The acetylene method has been validated
(2), and the cardiac
output-O2 relationship was similar in
the two groups (Fig. 3A), suggesting agreement. However, there may have been systematic differences between the two methods. We
therefore calculated the effect of potential errors in cardiac output
on estimated DLO2 and found that a 10%
error produces a 3.4% error in the same direction in estimated
DLO2. Thus to explain the 40% higher
DLO2 in the natives on errors in cardiac
output would require that peak cardiac output had been overestimated by
220% and was not 20 but only 9 l/min. This is impossible because even
complete muscle O2 extraction would not have provided the measured O2. If cardiac output in the
lowlanders had been lower because of blood withdrawal during its
measurement, this could have reduced estimated
DLO2. However, each measurement requires only 20 ml blood and moreover this was reinfused immediately. This
cannot therefore explain the lower lowlander
DLO2.
A specific assumption made in the calculation of
DLO2 is that ventilation-perfusion
(A/) inequality plays an insignificant role
in the (A-a)PO2 of exercise at this altitude.
Because neither group had an (A-a)PO2 at rest
(Fig. 1), resting A/ inequality must
have been minimal. Because effects of A/
inequality on (A-a)PO2 lessen with increasing
hypoxia, whereas those of diffusion limitation increase (11, 12,
21), the postulate that A/ inequality
during exercise contributed little to the
(A-a)PO2 is also reasonable. Work from
Operation Everest II (18), using the multiple inert gas
elimination technique to distinguish diffusion limitation from
A/ mismatching, confirmed that diffusion
limitation was the major contributor to the
(A-a)PO2.
Relating exercise DLO2 [119
ml/(min · Torr), lowlanders and 167 ml/(min · Torr),
natives] to maximal normoxic exercise capacity (282 W, lowlanders and
229 W, natives; Table 1) provides an astonishing result: The ratio of
pulmonary diffusing capacity to maximal normoxic power output is 0.73 ml/(min · Torr · W) in the natives and only 0.42 ml/(min · Torr · W) in the lowlanders. The natives
therefore have 173% of the diffusing capacity of the lowlanders per
watt of normoxic exercise capacity. It should be recalled that there were no differences in hemoglobin concentration to explain this (Table
1). This very large difference presumably stems from structural differences in their lungs. Whereas in the lowlanders (at sea level)
spirometry revealed vital capacity (111% predicted) and resting carbon
monoxide diffusing capacity (92% predicted) that were within normal
limits, vital capacity (134% predicted Caucasian sea-level values,
P < 0.01) and diffusing capacity (142% predicted, P < 0.001) were elevated in the natives when
referenced to North American norms. The high
DLO2 values in natives during exercise appear directionally compatible with these data and the literature (6, 15).
Acid-base balance during exercise. Despite similar blood Hb concentration, there appear to be acid-base control differences between the lowlanders and natives. As shown in Fig. 4, calculated base deficit rose linearly with lactate concentration in both groups, but with different slopes. The mean slope in the lowlanders (0.97 ± 0.02 meq/l per mmol/l lactate) is similar to values at sea level [for example, 1.03 in Operation Everest II (16) and 1.13 in the same Danish lowlanders studied later in Copenhagen] and is a reasonable (1:1) stoichiometric outcome. On the other hand, the slope in natives averaged only 0.81 ± 0.03, a highly significant (P < 0.001) difference implying greater lactate-buffering capacity. The explanation for these unexpected differences cannot be stated with certainty but may just reflect the Henderson-Hasselbalch equation: On the Davenport diagram, flattening of PCO2 isopleths occurs as PCO2 falls. Thus, at a lower PCO2, the change in pH (x-axis) for a given change in base deficit (y-axis) at constant PCO2 would be greater. The higher arterial PCO2 values in the natives (Fig. 2) are consistent with this idea. It is also possible that the natives may have had a larger blood volume, because lowlanders are known to reduce plasma volume at altitude. If this were the case, it could also have contributed to the better buffering of lactate in the natives.
Whatever the mechanism, the consequences for exercise limitation may be considerable. Recall that, atO2 max in
ambient air, lactate levels were higher in the natives (11.5 mmol/l)
than in the lowlanders (8.7 mmol/l). Had lowlander lactate levels been as high, arterial pH (at the same PCO2) would
have been 7.25 instead of 7.37 as measured. Combined with the severe
hypoxemia (73% saturation) and the evidence that ventilatory
stimulation was already great (PCO2 19 Torr, pH
7.37), it is likely that intolerable dyspnea would have occurred. We
therefore suggest that the relatively lower buffering capacity of the
lowlanders contributed to their exercise limitation.
In conclusion, this study, performed at 5,260 m, comparing Bolivian
high-altitude natives resident at La Paz (3,600-4,100 m) to
sea-level natives acclimatized for 9 wk at 5,260 m, has demonstrated a
number of pulmonary and other physiological differences between them.
1) Even 9 wk of residence at 5,260 m fails to accomplish complete normalization of arterial pH in lowlanders, and ventilation is
greater than expected from prior data. This raises the question of
whether full acclimatization at this altitude requires much longer than
previously suspected, possibly lifelong or even more than one
generation of exposure. 2) Reduced ventilatory response to
hypoxia in high-altitude natives, both at rest and during exercise, still occurs as in previous reports at lower altitudes, despite severe
acute arterial desaturation caused by rapid ascent from La Paz.
3) (A-a)PO2 values during exercise
are smaller in natives likely because of increased diffusing capacity
associated with larger lungs. This enables, at lower ventilatory cost,
the same arterial saturation as in lowlanders. When related to
metabolic potential assessed by maximal exercise capacity in normoxia,
pulmonary diffusing capacity is 73% greater per watt in natives than
in lowlanders. 4) Lactate buffering appears enhanced in
natives, defending arterial pH in the face of both higher lactate and
PCO2 levels than in acclimatized lowlanders.
| |
ACKNOWLEDGEMENTS |
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We thank Professor Carlos Aguirre from the Academia Nacional de
Ciencias de Bolivia and Dr. Pedro Miranda, Director of the Laboratorio
de Cósmica Fisica at Chacaltaya, where the experiments were
conducted, for invaluable help. The use of the facilities at the Club
Andino Boliviano was most valuable and appreciated. We also thank
SensorMedics for the use and support of the
O2 max system for measuring cardiac
output by acetylene uptake.
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FOOTNOTES |
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This study was supported by a grant from the Danish National Research Foundation (no. 504-14). Additional funding was obtained from the Carlsberg Foundation and the Copenhagen Muscle Research Centre. J. A. L. Calbet was on leave from the Department of Physical Education at the University of Las Palmas de Gran Canaria. P. D. Wagner and H. Wagner were supported in part by National Heart, Lung, and Blood Institute Grant HL-17731.
Address for reprint requests and other correspondence: P. D. Wagner, Div. of Physiology, Univ. of California, San Diego, 9500 Gilman Dr., MC 0623A, La Jolla, CA 92093 (E-mail: pdwagner{at}ucsd.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/japplphysiol.00093.2001
Received 30 January 2001; accepted in final form 9 November 2001.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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