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.

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.

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.

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.

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.