Ventilation and hypoxic ventilatory responsiveness in Chinese-Tibetan residents at 3,658m

Curran, Linda S., Jianguo Zhuang, Shin Fu Sun, and Lorna G. Moore. Ventilation and hypoxic ventilatory responsiveness inChinese-Tibetan residents at 3,658 m. J. Appl.Physiol. 83(6): 2098-2104, 1997.When breathingambient air at rest at 3,658 m altitude, Tibetan lifelong residents of3,658 m ventilate as much as newcomers acclimatized to high altitude;they also ventilate more and have greater hypoxic ventilatory responses(HVRs) than do Han ("Chinese") long-term residents at 3,658 m.This suggests that Tibetan ancestry is advantageous in protectingresting ventilation levels during years of hypoxic exposure and is ofinterest in light of the permissive role of hypoventilation in thedevelopment of chronic mountain sickness, which is nearly absent amongTibetans. The existence of individuals with mixed Tibetan-Chineseancestry (Han-Tibetans) residing at 3,658 m affords an opportunity totest this hypothesis. Eighteen men born in Lhasa, Tibet, China (3,658 m) to Tibetan mothers and Han fathers were compared with 27 Tibetan menand 30 Han men residing at 3,658 m who were previously studied. We usedthe same study procedures (minute ventilation was measured with adry-gas flowmeter during room air breathing and hyperoxia and with a13-liter spirometer-rebreathing system during the hypoxic andhypercapnic tests). During room air breathing at 3,658 m (inspired O₂ pressure = 93 Torr),Han-Tibetans resembled Tibetans in ventilation (12.1 ± 0.6 vs.11.5± 0.5 l/min BTPS,respectively) but had HVR that were blunted (63 ± 16 vs. 121 ± 13, respectively, for HVR shape parameterA) and declined with increasingduration of high-altitude residence. During administered hyperoxia(inspired O₂ pressure = 310 Torr)at 3,658 m, the paradoxical hyperventilation previously seen in Tibetanbut not Han residents at 3,658 m (11.8 ± 0.5 vs. 10.1 ± 0.5 l/min BTPS) was absent in theseHan-Tibetans (9.8 ± 0.6 l/minBTPS). Thus, although longerduration of high-altitude residence appears to progressively blunt HVRamong Han-Tibetans born and residing at 3,658 m, their Tibetan ancestryappears protective in their maintenance of high resting ventilationlevels despite diminished chemosensitivity.

     

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.     

Developmental,genetic, and environmental components of aerobic capacity at high altitude

The aerobic capacity of 268 subjects (158 males and 110 females) was evaluated in La Paz, Bolivia situated at 3,750 m. The sample included 1) 39 high altitude rural natives (all male); 2) 67 high altitude urban natives (32 male, 35 female); 3) 69 Bolivians of foreign ancestry acclimatized to high altitude since birth (37 male, 32 female); 4) 50 Bolivians of foreign ancestry acclimatized to high altitude during growth (25 male, 25 female); and 5) 43 non-Bolivians of either European or North American ancestry acclimatized to high altitude during adulthood (25 male, 18 female). Data analyses indicate that 1) high altitude urban natives, acclimatized to high altitude since birth or during growth, attained higher aerobic capacity than subjects acclimatized to high altitude during adulthood; 2) age at arrival to high altitude is inversely related to maximum oxygen consumption (V?O² max) expressed in terms L/min or ml/min/kg of lean body mass, but not in terms of ml/min/kg of body weight; 3) among subjects acclimatized to high altitude during growth, approximately 25% of the variability in aerobic capacity can be explained by developmental factors; 4) as inferred from evaluations of skin color reflectance and sibling similarities, approximately 20 to 25% of the variability in aerobic capacity at high altitude can be explained by genetic factors; 5) except among the non-Bolivians acclimatized to high altitude during adulthood, the aerobic capacity of individuals with high occupational activity level is equal to the aerobic capacity of high altitude rural natives; and 6) the relationship between occupational activity level and aerobic capacity is much greater among subjects acclimatized to high altitude before the age of 10 years than afterwards. Together these data suggest that the attainment of normal aerobic capacity at high altitude is related to both developmental acclimatization and genetic factors but its expression is highly mediated by environmental factors, such as occupational activity level and body composition. © 1995 Wiley-Liss, Inc.     

Maternal hypoxic ventilatory response, ventilation, and infant birth weight at 4,300 m

To test the hypothesis that increased hypoxic ventilatory responsiveness (HVR) raised maternal ventilation and arterial oxygenation during high-altitude pregnancy and related to the birth weight of the offspring, we studied 21 residents of Cerro de Pasco, Peru (4,300 m), while eight of them were 36 +/- 0 wk pregnant and 15 of them 13 +/- 0 wk postpartum. HVR was low in the nonpregnant women (mean +/- SE shape parameter A = 23 +/- 8) but increased nearly fourfold with pregnancy (A = 87 +/- 17). The increase in HVR appeared to account for the 25% rise in resting ventilation with pregnancy (delta VE observed = 2.4 +/- 0.7 l/min BTPS vs. delta VE predicted from delta HVR = 2.6 +/- 1.7 l/min BTPS, P = NS). Hyperoxia decreased ventilation in the pregnant women (P less than 0.01) to levels similar to those measured when nonpregnant. The increased ventilation of pregnancy raised arterial O2 saturation (SaO2) from 83 +/- 1 to 87 +/- 0%, and SaO2 was correlated positively with HVR in the pregnant women. The rise in SaO2 compensated for a 0.9 g/100 ml decrease in hemoglobin concentration to preserve arterial O2 content at levels present when nonpregnant. Cardiac output in the 36th wk of pregnancy did not differ significantly from values measured postpartum. The increase in HVR correlated positively with infant birth weight. An increase in HVR may be an important contributor to increased maternal ventilation with pregnancy and infant birth weight at high altitude.     

Superior exercise performance in lifelong Tibetan residents of 4,400 m compared with Tibetan residents of 3,658 m

Few environments challenge human populations more than high altitude, since the accompanying low oxygen pressures (hypoxia) are pervasive and impervious to cultural modification. Work capacity is an important factor in a population's ability to thrive in such an environment. The performance of work or exercise is a measure of the integrated functioning of the O₂ transport system, with maximal O₂ uptake (VO) a convenient index of that function. Hypoxia limits the ability to transport oxygen: maximal O₂ uptake decreases with ascent to high altitude, and years of high altitude residence do not restore sea level VO values. Since Tibetans live and work at some of the highest altitudes in the world, their ability to exercise at very high altitude (<4,000 m) may define the limits of human adaptation to hypoxia. We transported 20 Tibetan lifelong residents of ≥4,400 m down to 3,658 m in order to compare them with 16 previously studied Tibetan residents of Lhasa (3,658 m). The two groups of Tibetans were matched for age, weight, and height. All studies were performed in Lhasa within 3 days of the 4,400 m Tibetans' arrival. Standard test protocol and criteria were used for attaining VO on a Monark bicycle ergometer, while measuring oxygen uptake (VO₂, ml/kg − min STPD), heart rate (bpm), minute ventilation (VE, 1/min BTPS), and arterial oxygen saturation (Sa, %). The 4,400 m compared with 3,658 m residents had, at maximal effort, similar VO₂ (48.5 ± 1.2 vs. 51.2 ± 1.4 ml/kg − min, P = NS), higher workload attained (211 ± 6 vs. 177 ± 7 watts, P < 0.01), lower heart rate (176 ± 2 vs. 191 ± 2 bpm, P < 0.01), lower ventilation (127 ± 5 vs. 149 ± 5 l/min BTPS, P < 0.01), and similar Sa(81.9 ± 1.0 vs. 83.7 ± 1.2%, P = NS). Furthermore, over the range of submaximal workloads, 4,400 m compared with 3,658 m Tibetans had lower VO₂ (P < 0.01), lower heart rates (P < 0.01), and lower ventilation (P < 0.01) and Sa (P < 0.05). We conclude that Tibetans living at 4,400 m compared with those residing at 3,658 m achieve greater work performance for a given VO₂ at submaximal and maximal workloads with less cardiorespiratory effort. Am J Phys Anthropol 105:21–31, 1998. © 1998 Wiley-Liss, Inc.     

Effects of acute temperature changes on aerial and aquatic gas exchange, pulmonary ventilation and blood gas status in the South American lungfish, Lepidosiren paradoxa

Lungfish (Dipnoi) are probably sister group relative to all land vertebrates (Tetrapoda). The South American lungfish, Lepidosiren paradoxa, depends markedly on pulmonary gas exchange. In this context, we report on temperature effects on aquatic and pulmonary respiration, ventilation and blood gases at 15, 25 and 35 degrees C. Lung ventilation increased from 0.5 (15 degrees C) to 8.1 ml BTPS kg(-1) min(-1) (35 degrees C), while pulmonary O(2)-uptake increased from 0.06 (15 degrees C) to 0.73 ml STPD kg(-1) min(-1) (35 degrees C). Meanwhile aquatic O(2)-uptake remained about the same ( approximately 0.01 ml STPD kg(-1) min(-1)) at all temperatures. Concomitantly, the pulmonary gas exchange ratio (R(E)) rose from 0.11 (15 degrees C) to 0.62 (35 degrees C), because a larger fraction of total CO(2) output became eliminated by the lung. Accordingly, PaCO(2) rose from 13 (15 degrees C) to 37 mm Hg (35 degrees C), leading to a significant decrease of pHa at higher temperature (pHa=7.58-15 degrees C; 7.33-35 degrees C). The acid-base status of L. paradoxa was characterized by a generally low pH (7.4-7.5), high bicarbonate level (20-25 mM) and PaO(2) ( approximately 80 mm Hg). The increased dependence on the lung at higher temperature parallels data for amphibians. Further, the effects of bimodal gas exchange on temperature-dependent acid-base regulation closely resemble those of anuran amphibians.     

Increased vital and total lung capacities in Tibetan compared to Han residents of Lhasa (3,658 m).

Larger chest dimensions and lung volumes have been reported for Andean high-altitude natives compared with sea-level residents and implicated in raising lung diffusing capacity. Studies conducted in Nepal suggested that lifelong Himalayan residents did not have enlarged chest dimensions. To determine if high-altitude Himalayans (Tibetans) had larger lung volumes than acclimatized newcomers (Han "Chinese"), we studied 38 Tibetan and 43 Han residents of Lhasa, Tibet Autonomous Region, China (elevation 3,658 m) matched for age, height, weight, and smoking history. The Tibetan compared with the Han subjects had a larger total lung capacity [6.80 +/- 0.19 (mean +/- SEM) vs 6.24 +/- 0.18 l BTPS, P less than 0.05], vital capacity (5.00 +/- 0.08 vs 4.51 +/- 0.10 1 BTPS, P less than 0.05), and tended to have a greater residual volume (1.86 +/- 0.12 vs 1.56 +/- 0.09 1 BTPS, P less than 0.06). Chest circumference was greater in the Tibetan than the Han subjects (85 +/- 1 vs 82 +/- 1 cm, P less than 0.05) and correlated with vital capacity in each group as well as in the two groups combined (r = 0.69, P less than 0.05). Han who had migrated to high altitude as children (less than or equal to 5 years old, n = 6) compared to Han adult migrants (greater than or equal to 18 years old, n = 26) were shorter but had similar lung volumes and capacities when normalized for body size. The Tibetans' vital capacity and total lung capacity in relation to body size were similar to values reported previously for lifelong residents of high altitude in South and North America. Thus, Tibetans, like North and South American high-altitude residents, have larger lung volumes. This may be important for raising lung diffusing capacity and preserving arterial oxygen saturation during exercise.     

Individuality of breathing patterns during hypoxia and exercise.

Breathing was recorded via a pulsed ultrasonic flowmeter in 11 healthy subjects, at rest and during steady-state exercise (at 50% of their maximal O2 consumption) at both sea level (200 m) and simulated altitude (4,500 m in a hypobaric chamber). The pattern of breathing was quantified breath by breath in terms of classical respiratory variables (tidal volume and inspiratory and expiratory times), and the shape of the entire airflow profile was quantified by harmonic analysis. Statistical tests were used to compare the within-individual with the between-individual variations. In comparing the sea level vs. altitude rest (16% increase in ventilation) and sea level vs. altitude exercise (40% increase in ventilation) airflow profiles, we found a significantly greater resemblance within the individual than between individuals. Comparisons of sea level rest and exercise (295% increase in ventilation) and altitude rest and exercise (375% increase in ventilation) revealed no similarity within individuals. Despite airflow profile changes between rest and exercise, it is still possible to attest to a diversity of flow profile between individuals during exercise. Hypoxia at rest or during exercise does not alter the phenomenon of the individuality of breathing patterns.     

Climate, altitude, and blood pressure.

The effects of climate and altitude on casual blood pressure are examined from the perspectives of initial exposure, acclimatization, long-term residence, and birthplace. Hot arid and hot humid climates seem to have little effect on blood pressure, although a slight reduction may be found in some naturally acclimatized groups. Exposure of the total body to mild cold likewise has little apparent effect. Local exposure of the extremities to severe cold occasions significant increases in blood pressure during exposure but not at other times. Acclimatization reduces but does not eliminate that response. The effects of altitude on blood pressure are variable. There is initial hypertension, followed by gradual normalization. After years of residence at high altitude blood pressure may actually be lower than that observed among residents at sea level.     

Altitude acclimatization: influence on periodic breathing and chemoresponsiveness during sleep

Although the influence of altitude acclimatization on respiration has been carefully studied, the associated changes in hypoxic and hypercapnic ventilatory responses are the subject of controversy with neither response being previously evaluated during sleep at altitude. Therefore, six healthy males were studied at sea level and on nights 1, 4, and 7 after arrival at altitude (14,110 ft). During wakefulness, ventilation and the ventilatory responses to hypoxia and hypercapnia were determined on each occasion. During both non-rapid-eye-movement and rapid-eye-movement sleep, ventilation, ventilatory pattern, and the hypercapnic ventilatory response (measured at ambient arterial O2 saturation) were determined. There were four primary observations from this study: 1) the hypoxic ventilatory response, although similar to sea level values on arrival at altitude, increased steadily with acclimatization up to 7 days; 2) the slope of the hypercapnic ventilatory response increased on initial exposure to a hypoxic environment (altitude) but did not increase further with acclimatization, although the position of this response shifted steadily to the left (lower PCO2 values); 3) the sleep-induced decrements in both ventilation and hypercapnic responsiveness at altitude were equivalent to those observed at sea level with similar acclimatization occurring during wakefulness and sleep; and 4) the quantity of periodic breathing during sleep at altitude was highly variable and tended to occur more frequently in individuals with higher ventilatory responses to both hypoxia and hypercapnia.     

Effects of a 1-yr stay at altitude on ventilation, metabolism, and work capacity.

The hypoxic and hypercapnic ventilatory drive, gas exchange, blood lactate and pyruvate concentrations, acid-base balance, and physical working capacity were determined in three groups of healthy males: 17 residents examined at sea level (group I), 24 sea-level natives residing at 1,680-m altitude for 1 yr and examined there (group II), and 17 sea-level natives residing at 3,650-m altitude for 1 yr and examined there (group III). The piecewise linear approximation technique was used to study the ventilatory response curves, which allowed a separate analysis of slopes during the first phase of slow increase in ventilation and the second phase of sharp increase. The hypoxic ventilatory response for both isocapnic and poikilocapnic conditions was greater in group II and even greater in group III. The first signs of consciousness distortion in sea-level residents appeared at an end-tidal O2 pressure level (4.09 +/- 0.56 kPa) higher than that of temporary residents of middle (3.05 +/- 0.12) and high altitude (2.90 +/- 0.07). The hypercapnic response was also increased, although to a lesser degree. Subjects with the highest hypoxic respiratory sensitivity at high altitude demonstrated greater O2 consumption at rest, greater ventilatory response to exercise, higher physical capacity, and a less pronounced anaerobic glycolytic flux but a lower tolerance to extreme hypoxia. That is, end-tidal O2 pressure that caused a distortion of the consciousness was higher in these subjects than in those with lower hypoxic sensitivity. Two extreme types of adaptation strategy can be distinguished: active, with marked reactions of "struggle for oxygen," and passive, with reduced O2 metabolism, as well as several intermediate types.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of oxygen breathing on micro oxygen bubbles in nitrogen-depleted rat adipose tissue at sea level and 25 kPa altitude exposures

The standard treatment of altitude decompression sickness (aDCS) caused by nitrogen bubble formation is oxygen breathing and recompression. However, micro air bubbles (containing 79% nitrogen), injected into adipose tissue, grow and stabilize at 25 kPa regardless of continued oxygen breathing and the tissue nitrogen pressure. To quantify the contribution of oxygen to bubble growth at altitude, micro oxygen bubbles (containing 0% nitrogen) were injected into the adipose tissue of rats depleted from nitrogen by means of preoxygenation (fraction of inspired oxygen = 1.0; 100%) and the bubbles studied at 101.3 kPa (sea level) or at 25 kPa altitude exposures during continued oxygen breathing. In keeping with previous observations and bubble kinetic models, we hypothesize that oxygen breathing may contribute to oxygen bubble growth at altitude. Anesthetized rats were exposed to 3 h of oxygen prebreathing at 101.3 kPa (sea level). Micro oxygen bubbles of 500-800 nl were then injected into the exposed abdominal adipose tissue. The oxygen bubbles were studied for up to 3.5 h during continued oxygen breathing at either 101.3 or 25 kPa ambient pressures. At 101.3 kPa, all bubbles shrank consistently until they disappeared from view at a net disappearance rate (0.02 mm(2) × min(-1)) significantly faster than for similar bubbles at 25 kPa altitude (0.01 mm(2) × min(-1)). At 25 kPa, most bubbles initially grew for 2-40 min, after which they shrank and disappeared. Four bubbles did not disappear while at 25 kPa. The results support bubble kinetic models based on Fick's first law of diffusion, Boyles law, and the oxygen window effect, predicting that oxygen contributes more to bubble volume and growth during hypobaric conditions. As the effect of oxygen increases, the lower the ambient pressure. The results indicate that recompression is instrumental in the treatment of aDCS.     

Sleep deprivation and cardiorespiratory function. Influence of intermittent submaximal exercise

The effects of 64 h of sleep deprivation upon cardiorespiratory function was studied in 11 young men (VO2max = 55.5 ml kg-1 min-1, STPD). Six subjects engaged in normal sedentary activities, while the others walked on a treadmill at 28% VO2max for one hour in every three; eight weeks later, sleep deprivation was repeated with a crossover of subjects. Immediate post-deprivation measurement of VO2max showed a small but statistically significant decrease (-3.8 ml min-1 kg-1, STPD), with no difference between exercise and control trials. The final decrement in aerobic power was not due to a loss of motivation, as 88% (21 of 24) of post-deprivation tests still showed a plateau of VO2max; in addition, terminal heart rates (198 vs 195 beats min-1), respiratory exchange ratios (1.14 vs 1.15) and blood lactate levels (12.1 vs 11.8 mmol l-1) were not significantly different after sleep deprivation. The decrease in VO2max was associated with a lower VEmax (127 vs 142 l min-1, BTPS) and a substantial haemodilution (13%). Physiological responses to sub-maximal exercise showed persistence of the normal diurnal rhythm in heart rate and oxygen consumption, with no added effects due to sleep deprivation. However, ratings of perceived exertion (Borg scale) increased significantly throughout sleep deprivation. The findings are consistent with a mild respiratory acidosis, secondary to reduced cortical arousal and/or a progressive depletion of tissue glycogen stores which are not altered appreciably by moderate physical activity.     

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.     

The pattern of breathing and the ventilatory response to breathing through a tube and to physical exercise in sport divers

Well-trained divers can be expected to differ from healthy controls in their ventilatory response to breathing through a tube and to physical exercise. Therefore, we measured their minute ventilation (VE) at rest and during breathing through a tube combined with two levels of physical exercise (1 or 2 W.kg body weight-1). For breathing through a tube an additional dead space of 600 ml was used. All divers were trained in the breath-hold technique and in the use of the breathing apparatus. Their mean period of training as divers was 9 +/- 6 years. The approximate age of the subjects was 25 years. The pattern of breathing and the oxygen uptake were measured by spirometer, the end-tidal concentration of CO2 was measured and all experiments were carried out above sea level. The ventilation of the divers at rest was comparable to that of the controls. During physical exercise it was smaller whether during breathing through a tube or not. The inadequate increase of VE during exercise in divers was associated with hypercapnia only at a higher physical work intensity (of 2 W.kg-1). This finding is interpreted as a lower chemoregulatory response to the combined stimuli of hypercapnia, hypoxia and physical exercise. In some situations significant bradypnoea and higher tidal volumes were found in the divers.     

Respiratory energetics during exercise at high altitude.

The purpose of this study was to assess the effect of high altitude (HA) on work of breathing and external work capacity. On the basis of simultaneous records of esophageal pressure and lung volume, the mechanical power of breathing (Wrs) was measured in four normal subjects during exercise at sea level (SL) and after a 1-mo sojourn at 5,050 m. Maximal exercise ventilation (VEmax) and maximal Wrs were higher at HA than at SL (mean 185 vs. 101 l/min and 129 vs. 40 cal/min, respectively), whereas maximal O2 uptake averaged 2.07 and 3.03 l/min, respectively. In three subjects, the relationship of Wrs to minute ventilation (VE) was the same at SL and HA, whereas, in one individual, Wrs for any given VE was consistently lower at HA. Assuming a mechanical efficiency (E) of 5%, the O2 cost of breathing at HA and SL should amount to 26 and 5.5% of maximal O2 uptake, whereas for E of 20% the corresponding values were 6.5 and 1.4%, respectively. Thus, at HA, Wrs may substantially limit external work unless E is high. Although at SL VEmax did not exceed the critical VE, at which any increase in VE is not useful in terms of body energetics even for E of 5%, at HA VEmax exceeded critical VE even for E of 20%.     

"Living high-training low" altitude training improves sea level performance in male and female elite runners.

Acclimatization to moderate high altitude accompanied by training at low altitude (living high-training low) has been shown to improve sea level endurance performance in accomplished, but not elite, runners. Whether elite athletes, who may be closer to the maximal structural and functional adaptive capacity of the respiratory (i.e., oxygen transport from environment to mitochondria) system, may achieve similar performance gains is unclear. To answer this question, we studied 14 elite men and 8 elite women before and after 27 days of living at 2,500 m while performing high-intensity training at 1,250 m. The altitude sojourn began 1 wk after the USA Track and Field National Championships, when the athletes were close to their season's fitness peak. Sea level 3,000-m time trial performance was significantly improved by 1.1% (95% confidence limits 0.3-1.9%). One-third of the athletes achieved personal best times for the distance after the altitude training camp. The improvement in running performance was accompanied by a 3% improvement in maximal oxygen uptake (72.1 +/- 1.5 to 74.4 +/- 1.5 ml x kg(-1) x min(-1)). Circulating erythropoietin levels were near double initial sea level values 20 h after ascent (8.5 +/- 0.5 to 16.2 +/- 1.0 IU/ml). Soluble transferrin receptor levels were significantly elevated on the 19th day at altitude, confirming a stimulation of erythropoiesis (2.1 +/- 0.7 to 2.5 +/- 0.6 microg/ml). Hb concentration measured at sea level increased 1 g/dl over the course of the camp (13.3 +/- 0.2 to 14.3 +/- 0.2 g/dl). We conclude that 4 wk of acclimatization to moderate altitude, accompanied by high-intensity training at low altitude, improves sea level endurance performance even in elite runners. Both the mechanism and magnitude of the effect appear similar to that observed in less accomplished runners, even for athletes who may have achieved near maximal oxygen transport capacity for humans.     

Alkaline shift in lumbar and intracranial CSF in man after 5 days at high altitude.

In six healthy male volunteers at sea level (PB 747-759 Torr), we measured pH and PCO2 in cerebrospinal fluid (CSF), and in arterial and jugular bulb blood; from these data we estimated PCO2 (12) and pH for the intracranial portion of CSF. The measurements were repeated after 5 days in a hypobaric chamber (PB 447 Torr). Both lumbar and intracranial CSF were significantly more alkaline at simulated altitude than at sea level. Decrease in [HCO3-] IN lumbar CSF at altitude was similar to that in blood plasma. Both at sea level and at high altitude, PCO2 measured in the lumbar CSF was higher than that estimated for the intracranial CSF. At altitude, hyperoxia, in comparison with breathing room air, resulted in an increase in intracranial PCO2, and a decrease in the estimated pH in intracranial CSF. With hyperoxia at altitude, alveolar ventilation was significantly higher than during sea-level hyperoxia or normoxia, confirming that a degree of acclimatization had occurred. Changes in cerebral arteriovenous differences in CO2, measured in three subjects, suggest that cerebral blood flow may have been elevated after 5 days at altitude.     

The 1988 Stevenson Memorial lecture. Physiological responses to severe hypoxia in man

Recent measurements at extreme altitude and in low pressure chamber simulations have clarified the human responses to extreme hypoxia. Man can only tolerate the severe oxygen deprivation of great altitudes by an enormous increase in ventilation which has the advantage of defending the alveolar PO2 against the reduced inspired PO2. Nevertheless the arterial PO2 on the Everest summit is less than 30 Torr (1 Torr = 133.3 Pa). An interesting consequence of the hyperventilation is that the respiratory alkalosis greatly increases the oxygen affinity of the hemoglobin and assists in oxygen loading by the pulmonary capillary. The severe hypoxemia impairs the function of many organ systems including the central nervous system, and there is evidence of residual impairment of memory and manipulative skill in climbers returning from great altitudes. At the altitude of Mt. Everest, maximal oxygen uptake is reduced to 20-25% of its sea level value, and it is exquisitely sensitive to barometric pressure. It is likely that the seasonal variation of barometric pressure affects the ability of man to reach the summit without supplementary oxygen.