Tibetan protection from intrauterine growth restriction (IUGR) and reproductive loss at high altitude.

Chronic hypoxia at high altitude restricts fetal growth, reducing birth weight and increasing infant mortality. We asked whether Tibetans, a long-resident high-altitude population, exhibit less altitude-associated intrauterine growth restriction (IUGR) and prenatal or postnatal reproductive loss than Han (ethnic Chinese), a group that has lived there for a shorter period of time. A population sample was obtained, comprising 485 deliveries to Tibetan or Han women over an 18-month period at 8 general hospitals or clinics located at 2,700-4,700 m in the Tibet Autonomous Region, China. Birth weight, gestational age, and other information were recorded for each delivery. Prenatal and postnatal mortality were calculated using information obtained from all pregnancies or babies born to study participants. Tibetan babies weighed more than the Han, averaging 310 g heavier at altitudes 2,700-3,000 m (95% CI = 126, 494 g; P < 0.01) and 530 g heavier at 3,000-3,800 m (210, 750 g; P < 0.01). More Han than Tibetan babies were born prematurely. Prenatal and postnatal mortality rose with increasing elevation and were 3-fold higher across all altitudes in the Han than the Tibetans (P < 0.05). Tibetans experience less altitude-associated IUGR than Han and have lower levels of prenatal and postnatal mortality. When the relationships between birth weight and altitude are compared among these and other high-altitude populations, those living at high altitude the longest have the least altitude-associated IUGR. This may suggest the occurrence of an evolutionary adaptation.

Oxygen transport in tibetan women during pregnancy at 3,658 m.

High-altitude reduces infant birth weight as a result of intrauterine growth restriction (IUGR) and is associated with increased neonatal mortality. We hypothesized that babies born to Tibetan compared to Han (Chinese) high-altitude residents were protected from IUGR as the result of increased maternal O(2) transport due, in turn, to increased uterine artery (UA) blood flow. We studied 68 nonpregnant or pregnant Tibetan or Han residents of Lhasa, Tibet Autonomous Region, China (3,658 m). The pregnant women had higher hypoxic ventilatory responses (HVR A) and resting ventilations (V(E)) than their nonpregnant counterparts (Tib HVR = 134 +/- 16 (SEM) vs. 30 +/- 8, Han HVR = 134 +/- 16 vs. 66 +/- 18 A units; Tib V(E) = 11.8 +/- 0.3 vs. 10.1 +/- 0.5, Han V(E) = 10.7 +/- 0.5 vs. 9.4 +/- 0.5 l BTPS/min; all P < 0.05). Pregnancy did not change hemoglobin concentration in the Han but lowered values more than 2 g/dl in the Tibetans, serving to reduce arterial O(2) content below Han values (15.4 +/- 0.3 vs. 17.4 +/- 0.5 ml O(2)/100 ml whole blood, P < 0.05). Compared with the Han, the pregnant Tibetans had higher UA blood flow velocity (58.5 +/- 2.9 vs. 49.1 +/- 3.2, P < 0. 05) and distributed a higher portion of common iliac (CI) blood flow to the UA (4.8 +/- 0.4 vs. 3.3 +/- 0.3, P < 0.05). Birth weights averaged 635 g greater in the Tibetan than Han high-altitude residents (3,280 +/- 78 vs. 2,645 +/- 96 g, P < 0.01), or 694 g more when adjusted for maternal age, parity, height, and near-term body weight. Heavier birth weight babies were born to women with higher V(E) (r = 0.62, P < 0.01) and greater distribution of CI blood flow to the UA (r = 0.42, P < 0.05). We conclude that increased UA blood flow, and not higher arterial O(2) content, permits Tibetan women to increase uteroplacental O(2) delivery and protect their infants from altitude-associated IUGR.

ECG observations in Tibetan and Han residents of Lhasa.

In order to compare the prevalence of electrocardiographic (ECG) abnormalities suggestive of right ventricular hypertrophy in native and immigrant populations residing at high altitude, a retrospective review was undertaken of data obtained from a random survey of healthy volunteers and persons with chronic mountain sickness (CMS). All persons included in the survey were ambulatory volunteers from the general community who were evaluated at the Tibet Institute of Medical Science in Lhasa, where the elevation is 3,658 meters. The 74 residents of Lhasa, whose ECGs were studied, included 30 healthy Tibetan natives of Lhasa; 24 healthy Han (Chinese) immigrants, born at or near sea level, who had migrated to high altitude as children or adults; and 20 persons with symptoms of CMS. The ECGs of all subjects were reviewed for predetermined criteria suggestive of right ventricular hypertrophy, which were found to be present in 17% of healthy Tibetan natives, 29% of healthy Han immigrants, and 50% of CMS patients. The Han subjects who had migrated as children presented evidence of right ventricular hypertrophy more commonly than did adult immigrants. The overwhelming majority (90%) of persons with CMS were Han. Thus, the frequency of ECG abnormalities consistent with right ventricular hypertrophy was similar in healthy young Tibetan and Han men, but these abnormalities were less common in Tibetan natives than in Han who had migrated to high altitude as children or in CMS patients. The prevalence of ECG evidence of right ventricular hypertrophy increased with duration of high altitude residence among Han.

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 (.VO2max) 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 .VO2max 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 > or =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 .VO2max 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 (SaO2, %). 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 SaO2(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 SaO2 (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.

Breathing and brain blood flow during sleep in patients with chronic mountain sickness.

Chronic mountain sickness (CMS) patients have lower arterial O2 saturation (SaO2) during sleep compared with healthy high-altitude residents, but whether nocturnal arterial O2 content (CaO2) and brain O2 delivery are reduced is unknown. We measured SaO2, CaO2, sleep-disordered breathing (SDB), and internal carotid artery flow velocity in 8 CMS patients, 8 age-matched healthy CMS controls, 11 healthy younger-aged Han, and 11 healthy younger-aged Tibetan male residents of Lhasa, Tibet (3,658 m). CMS patients spent a greater portion of the night in SDB (total no. of episodes of apnea, hypopnea, and hypoventilation) than did the CMS controls, young Han, or young Tibetans (15% vs. 5, 1, and 1%, respectively; P < 0.05) because of more frequent apnea and hypoventilation episodes and longer duration of all types of episodes. SDB and unexplained arterial O2 desaturation caused nocturnal SaO2 to be lower and more variable in CMS patients than in CMS controls or in younger-aged Han or Tibetan men. Average CaO2 was similar, but the CMS patients spent 29%, whereas the other groups spent < 4%, of the night at values < 18 ml O2/100 ml whole blood. Internal carotid artery flow velocity during wakefulness was similar in CMS patients and CMS controls despite higher end-tidal PcO2 values in the CMS patients. When contiguous sleep stages are compared, flow velocity rose from stage 2 to rapid-eye-movement sleep in both groups. Whereas flow velocity remained elevated from awake to rapid-eye-movement sleep in the CMS controls, it fell in the CMS patients. During episodes of SDB, internal carotid flow velocity increased in CMS controls but did not change in the CMS patients such that values were lower in the CMS patients than in CMS controls at the end and after SDB episodes. We concluded that SDB and episodes of unexplained desaturation lowered nocturnal SaO2 and CaO2, which, together with a lack of compensatory increase in internal carotid artery flow velocity, likely decreased brain O2 delivery in CMS patients during a considerable portion of the night.

Smaller alveolar-arterial O2 gradients in Tibetan than Han residents of Lhasa (3658 m).

Previous studies have indicated that native Tibetans have a larger lung capacity and better maintain arterial O2 saturation during exercise than Han ("Chinese") acclimatized lowlanders. To test if differences in ventilation or alveolar-arterial O2 gradient (A-aDO2) were responsible, we compared 10 lifelong Tibetan and 9 Han acclimatized newcomer residents of Lhasa (3658 m) at rest and during progressive exercise. Resting blood gas tensions and arterial O2 saturation in the two groups were similar. During exercise the Tibetans had lower total ventilation and higher arterial CO2 tensions than the Han (both P < 0.01) and markedly lower A-aDO2 (7 +/- 1 vs. 11 +/- 1, 13 +/- 1 vs. 18 +/- 1, and 14 +/- 1 vs. 20 +/- 1 mmHg at light, medium, and heavy workloads respectively, all P < 0.01). The Tibetans' narrower A-aDO2 compensated for their lower exercise ventilation such that arterial O2 tension and saturation were raised above acclimatized newcomer values and better maintained during exercise. We concluded that the Tibetans exhibited more efficient pulmonary gas exchange which compensated for reduced ventilation and lessened respiratory effort.

Effect of altitude on uterine artery blood flow during normal pregnancy.

To determine whether uterine blood flow was reduced and indexes of pelvic blood flow distribution altered in normotensive pregnancy at high (3,100 m) compared with low altitude (1,600 m), we measured uterine, common iliac, and external iliac artery blood flow velocities and diameters in women during pregnancy and again postpartum. Pregnancy increased uterine artery diameter, blood flow velocity, and volumetric flow at both altitudes. Uterine artery blood flow velocity was greater (69.0 +/- 2.2 vs. 59.4 +/- 3.0 cm/s; P < 0.005) but diameter was smaller at 3,100 m than at 1,600 m (2.5 +/- 0.3 mm vs. 3.4 +/- 0.2 mm; P < 0.005), resulting in volumetric flow that was one-third lower at week 36 of pregnancy (203 +/- 48 vs. 312 +/- 22 ml/min, respectively; P < 0.01). Pregnancy increased common iliac blood flow velocity and decreased external iliac artery blood flow velocity at both altitudes. The uterine artery received a smaller percent of common iliac flow at 3,100 than at 1,600 m (46 +/- 7 vs. 74 +/- 6%; P < 0.005). Gestational age was similar but birth weight was lower at 3,100 m than at 1,600 m. Among subjects at 1,600 m, variation in uterine blood flow velocity correlated positively with infant birth weight. We concluded that reduced uterine blood flow and altered pelvic blood flow distribution during pregnancy at high altitude likely contributed to the altitude-associated reduction in infant birth weight.

Hypoxic ventilatory responses in Tibetan residents of 4400 m compared with 3658 m.

Lifelong Tibetan residents of 3658 m ventilate as much and have hypoxic and hypercapnic ventilatory responsiveness as least as great as acclimatized newcomers, and likely greater than lifelong North or South American high-altitude residents. To determine whether Tibetans residing at altitudes > 3658 m maintained similar levels of ventilation, hypoxic and hypercapnic ventilatory responses, we transported 20 lifelong residents of > or = 4400 m to 3658 m for comparison with 27 similarly-aged male Tibetan residents of 3658 m. At 3658 m, the 4400 m compared with the 3658 m Tibetans had similar levels of minute ventilation and arterial O2 saturation, higher respiratory quotients but lower hypoxic ventilatory responses. We conclude that Tibetan residents of > or = 4400 m ventilate as much as Tibetan residents of 3658 m despite an altitude-associated blunting of their hypoxic ventilatory responses. Thus, factors other than hypoxic ventilatory chemosensitivity are likely to be important contributors to resting ventilation among Tibetan high altitude residents.

Mitochondrial DNA analysis in Tibet: implications for the origin of the Tibetan population and its adaptation to high altitude.

Mitochondrial DNAs (mtDNAs) of 54 Tibetans residing at altitudes ranging from 3,000-4,500 m were amplified by polymerase chain reaction (PCR), examined by high-resolution restriction endonuclease analysis, and compared with those previously described in 10 other Asian and Siberian populations. This comparison revealed that more than 50% of Asian mtDNAs belong to a unique mtDNA lineage which is found only among Mongoloids, suggesting that this lineage most likely originated in Asia at an early stage of the human colonization of that continent. Within the Tibetan mtDNAs, sets of additional linked polymorphic sites defined seven minor lineages of related mtDNA haplotypes (haplogroups). The frequency and distribution of these haplogroups in modern Asian populations are supportive of previous genetic evidence that Tibetans, although located in southern Asia, share common ancestral origins with northern Mongoloid populations. This analysis of Tibetan mtDNAs also suggests that mtDNA mutations are unlikely to play a major role in the adaptation of Tibetans to high altitudes.

Autonomic regulation of heart rate response to exercise in Tibetan and Han residents of Lhasa (3,658 m).

To test the hypothesis that native high-altitude residents have less beta-sympathetic and more parasympathetic tone than newcomers, we compared the effects of beta-sympathetic and parasympathetic blockade in 10 Tibetan and 9 Han acclimatized male residents of Lhasa, Tibet Autonomous Region, China (elevation 3,658 m). Each subject was studied during cycle ergometer exercise at 70, 132, and 191 W after placebo (normal saline), beta-sympathetic (propranolol, 0.2 mg/kg iv), or parasympathetic (atropine, 0.04 mg/kg iv) blockade in random order on different days. At rest, the fall in resting heart rate with propranolol and the rise with atropine were equal in Tibetan and Han subjects. During exercise, the fall in heart rate with propranolol relative to placebo values was greater in the Han than in the Tibetan group, whereas the rise in heart rate with atropine was greater in the Tibetans. Propranolol or atropine administration did not change minute ventilation per unit O2 consumption in either group. At the highest level of exercise on the placebo day, the Tibetans achieved a higher work load and level of O2 consumption than the Han subjects. Propranolol or atropine reduced O2 consumption and work load similarly in the two groups at the highest exercise level. The results supported our hypothesis that native Tibetan residents of high altitude exhibit more para-sympathetic and less beta-sympathetic tone during exercise. Neither relatively greater parasympathetic nor less sympathetic activation appeared implicated in the greater exercise capacity of Tibetans compared with that of acclimatized newcomer residents of high altitude.

Protection from intrauterine growth retardation in Tibetans at high altitude.

Intrauterine growth retardation has long been recognized at high altitude. Since growth-retarded babies have a decreased chance of survival, intrauterine growth retardation would be expected to have been selected against in populations long resident at high altitude. We have previously reported that Tibetan babies born at 3,658 m weighed more than their North or South American altitude counterparts. This study sought to determine whether Tibetans were protected from altitude-associated intrauterine growth retardation. We compared birth weights in Tibetans living at low altitude in Kathmandu, Nepal (elevation 1,200 m), or at high altitude in Lhasa, Tibet Autonomous Region, China (elevation 3,658 m). Birth weights were similar in 45 low-altitude and 34 high-altitude Tibetan births regardless of whether all infants or only full-term births were considered, or whether birth weight was adjusted for variation in maternal parity, gestational age, and infant sex. In comparison with literature observations, the altitude-associated difference in birth weight was smallest in Tibetans, intermediate in South America, and greatest in North America. These data support the hypothesis that Tibetans are protected from altitude-associated intrauterine growth retardation and suggest that selection for optimization of birth weight at high altitude has occurred in Tibetans.

PIP: Researchers compared data on infants born to 45 Tibetan women who delivered at the Patan Hospital in Kathmandu, Nepal (1200 m), in 1990 with data on 34 infants born to Tibetan women who delivered at the People's Provincial Hospital in Lhasa (3658 m) in the Tibet Autonomous Region of China in 1987-1988 and in 1991. All the women were healthy. The aim of the study was to determine whether birth weight differs in Tibetans born at low altitude compared with those born at high altitude. The mean birth weight of all Tibetan infants born at high altitude essentially matched that of those born at low altitude (3222 g and 3313 g, respectively). Further, the 2 groups exhibited similar weight gain as gestational age increased. The frequency of preterm post-term and low-birth-weight infants and mean gestational age were essentially the same for both high and low altitude infants. The researchers compared this study's results with those from studies in high altitude areas of Bolivia, Peru, and Colorado, USA. Tibetans had the smallest attitude associated difference in birth weight, followed by infants in South America and then by infants in the US (72 g, 282-270 g, and 352 g, respectively). In fact, the altitude associated differences in birth weight in South America and the US were significant (p .01) while they were not significant in Tibetans. These findings strongly suggested that Tibetans have experienced natural selection for optimization of birth weight at high altitude. They supported the hypothesis that genetic adaptation protects Tibetans from altitude associated intrauterine growth retardation.

Hypoxic ventilatory responsiveness in Tibetan compared with Han residents of 3,658 m.

Lifelong high-altitude residents of North and South America acquire blunted hypoxic ventilatory responses and exhibit decreased ventilation compared with acclimatized newcomers. The ventilatory characteristics of Himalayan high-altitude residents are of interest in the light of their reportedly lower hemoglobin levels and legendary exercise performance. Until recently, Sherpas have been the only Himalayan population available for study. To determine whether Tibetans exhibited levels of ventilation and hypoxic ventilatory drives that were as great as acclimatized newcomers, we compared 27 lifelong Tibetan residents of Lhasa, Tibet, China (3,658 m) with 30 acclimatized Han ("Chinese") newcomers matched for age, body size, and extent of exercise training. During room air breathing, minute ventilation was greater in the Tibetan than in the Han young men because of an increased respiratory frequency, but arterial O2 saturation and end-tidal PCO2 did not differ, indicating similar levels of effective alveolar ventilation. The Tibetan subjects had higher hypoxic ventilatory response shape parameter A values and hypercapnic ventilatory responsiveness than the Han subjects. Among the Han subjects, duration of high-altitude residence correlated with the degree of blunting of the hypoxic ventilatory drive. Paradoxically, hyperoxia (inspired O2 fraction 0.70) increased minute ventilation and decreased end-tidal PCO2 in the Tibetan but not in the Han men. We concluded that lifelong Tibetan residents of high altitude neither hypoventilated nor exhibited blunted hypoxic ventilatory responses compared with acclimatized Han newcomers, suggesting that the effects of lifelong high-altitude residence on ventilation and ventilatory response to hypoxia differ in Tibetan compared with other high-altitude populations.

Minimal hypoxic pulmonary hypertension in normal Tibetans at 3,658 m.

Elevated pulmonary arterial pressure in high-altitude residents may be a maladaptive response to chronic hypoxia. If so, well-adapted populations would be expected to have pulmonary arterial pressures that are similar to sea-level values. Five normal male 22-yr-old lifelong residents of > or = 3,600 m who were of Tibetan descent were studied in Lhasa (3,658 m) at rest and during near-maximal upright ergometer exercise. We found that resting mean pulmonary arterial pressure [15 +/- 1 (SE) mmHg] and pulmonary vascular resistance (1.8 +/- 0.2 Wood units) were within sea-level norms and were little changed while subjects breathed a hypoxic gas mixture [arterial O2 pressure (PaO2) = 36 +/- 2 Torr]. Near-maximal exercise [87 +/- 13% maximal O2 uptake (VO2max)] increased cardiac output more than threefold to values of 18.3 +/- 1.2 l/min but did not elevate pulmonary vascular resistance. Breathing 100% O2 during near-maximal exercise did not reduce pulmonary arterial pressure or vascular resistance. We concluded that this small sample of healthy Tibetans with lifelong residence > or = 3,658 m had resting pulmonary arterial pressures that were normal by sea-level standards and exhibited minimal hypoxic pulmonary vasoconstriction, both at rest and during exercise. These findings are consistent with remarkable cardiac performance and high-altitude adaptation.

Internal carotid arterial flow velocity during exercise in Tibetan and Han residents of Lhasa (3,658 m).

Cerebral blood flow increases with acute exposure to high altitude, but the effect of hypoxia on the cerebral circulation at rest and during exercise appears influenced by the duration of high-altitude exposure. To determine whether internal carotid artery flow velocity increased with exercise in long-term residents of high altitude and whether resting values and the response to exercise differed in lifelong vs. acclimatized newcomer male residents of high altitude, we studied 15 native Tibetan and 11 Han ("Chinese") 6 +/- 2-yr residents of Lhasa (3,658 m), Tibet Autonomous Region, China. Noninvasive Doppler ultrasound was used to measure internal carotid artery diameter, mean flow velocity, and, in combination, hemoglobin and arterial O2 saturation to assess cerebral O2 delivery. Tibetan and Han groups were similar in body size and resting internal carotid artery diameter, blood pressure, hemoglobin concentration, internal carotid artery mean flow velocity, and calculated cerebral O2 delivery. Submaximal exercise increased internal carotid artery mean flow velocity and cerebral O2 delivery in the Tibetan and Han subjects. At peak exercise, the Tibetans sustained the increase in flow velocity and cerebral O2 delivery, whereas the Hans did not. Across all exercise levels up to and including peak effort, the Tibetans demonstrated a greater increase in internal carotid artery flow velocity and cerebral O2 delivery relative to resting values than did the Hans. The greater cerebral O2 delivery was accompanied by increased peak exercise capacity in the Tibetan compared with the Han group. Our findings suggest that the cerebral blood flow response to exercise is maintained in Tibetan lifelong residents of high altitude.

Are Tibetans better adapted?

Evidence is reviewed from our recent (1987-1991) investigations which demonstrate better high-altitude adaptation among Tibetans than in acclimatized newcomers or other lifelong high-altitude residents. Characteristics of oxygen transport contributing to the Tibetans' remarkable exercise performance are described.

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.

Decreased ventilation and hypoxic ventilatory responsiveness are not reversed by naloxone in Lhasa residents with chronic mountain sickness.

Persons with chronic mountain sickness (CMS) hypoventilate and are more hypoxemic than normal individuals, but the cause of the hypoventilation is unclear. Studies of 14 patients with CMS and 11 healthy age-matched control subjects residing in Lhasa, Tibet, China (3,658 m) were conducted to test the hypothesis that hypoventilation, blunted hypoxic ventilatory responsiveness (HVR), and hypoxic ventilatory depression of CMS were due to increased endogenous opioid production. Patients with CMS compared with control subjects exhibited hypoventilation (end-tidal carbon dioxide pressure [PETCO2] = 36.6 +/- 1.0 versus 31.5 +/- 0.5 mm Hg, p less than 0.05), lower tidal volume (VT = 0.54 +/- 0.02 versus 0.61 +/- 0.02 ml BTPS, p less than 0.05), blunted HVR (shape parameter A = 17 +/- 8 versus 114 +/- 22 mm Hg/L BTPS/min, p less than 0.05), and a depressant effect of ambient hypoxia on ventilation (delta PETCO2 with acute hyperoxia = -3.5 +/- 0.5 versus -1.0 +/- 0.6 mm Hg, p less than 0.05). Reduced forced expiratory volume in 1 s to vital capacity ratios (FEV1/VC) and a higher proportion of cigarette smokers in the group of patients with CMS compared with control subjects suggested that at least some patients with CMS had mild airway obstructive lung disease. Naloxone infusion (0.14 mg/kg) to six patients with CMS did not change resting VT, PETCO2, HVR, or SaO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Greater maximal O2 uptakes and vital capacities in Tibetan than Han residents of Lhasa.

Maximal O2 uptake provides an index of the integrated functioning of the O2 transport system. Whether lifelong high altitude residents have greater maximal exercise capacities than acclimatized newcomers is of interest for determining whether years to generations of high altitude exposure influence maximal O2 uptake and, if so, what components of O2 transport are involved. We studied 16 Tibetan lifelong residents of Lhasa, Tibet, China (3658 m) and 20 Han ("Chinese") 8 +/- 1 year residents of the same altitude who were matched for age, height, weight and lack of exercise training. At maximal effort, the Tibetans compared to the Hans had greater O2 uptakes (51 +/- 1 vs 46 +/- 1 ml STPD.min-1.(kg bw)-1, P less than 0.05), exercise workloads (177 +/- 5 vs 155 +/- 6 watts, P less than 0.05), minute ventilations (149 +/- 6 vs 126 +/- 4 IBTPS/min, P less than 0.01) and O2 pulse (15.2 +/- 0.4 vs 13.3 +/- 0.5 ml O2 consumption/heart beat, P less than 0.05). Equally high heart rates were present at maximal effort (191 +/- 3 vs 187 +/- 3 beats/min, P = NS), supporting the likelihood that true maxima were achieved in both groups. The greater minute ventilation in the Tibetans resulted from greater tidal volume and the greater maximal tidal volume correlated positively with the resting vital capacity. We concluded that the Tibetans achieved a higher maximal O2 uptake than the Hans, implying an increased capacity for O2 transport to the working muscle.