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.

Arterial O2 delivery during short-term submaximal exercise falls on arrival at high altitude but thereafter remains constant. As arterial O2 content increases with acclimatization, blood flow falls. We evaluated several factors that could influence O2 delivery during more prolonged submaximal exercise after acclimatization at 4,300 m. Seven men (23 +/- 2 yr) performed 45 min of steady-state submaximal exercise at sea level (barometric pressure 751 Torr), on acute ascent to 4,300 m (barometric pressure 463 Torr), and after 21 days of residence at altitude. The O2 uptake (VO2) was constant during exercise, 51 +/- 1% of maximal VO2 at sea level, and 65 +/- 2% VO2 at 4,300 m. After acclimatization, exercise cardiac output decreased 25 +/- 3% compared with arrival and leg blood flow decreased 18 +/- 3% (P less than 0.05), with no change in the percentage of cardiac output to the leg. Hemoglobin concentration and arterial O2 saturation increased, but total body and leg O2 delivery remained unchanged. After acclimatization, a reduction in plasma volume was offset by an increase in erythrocyte volume, and total blood volume did not change. Mean systemic arterial pressure, systemic vascular resistance, and leg vascular resistance were all greater after acclimatization (P less than 0.05). Mean plasma norepinephrine levels also increased during exercise in a parallel fashion with increased vascular resistance. Thus we conclude that both total body and leg O2 delivery decrease after arrival at 4,300 m and remain unchanged with acclimatization as a result of a parallel fall in both cardiac output and leg blood flow and an increase in arterial O2 content.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Reduced tolerance to high altitude may be associated with a low ventilatory and an increased pulmonary vascular response to hypoxia. We therefore, examined whether individuals susceptible to acute mountain sickness (AMS) or high altitude pulmonary oedema (HAPE) could be identified by noninvasive measurements of these parameters at low altitude. Ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) at rest and during exercise, as well as hypoxic pulmonary vascular response (HPVR) at rest, were examined in 30 mountaineers whose susceptibility was known from previous identical exposures to high altitude. Isocapnic HVR expressed as difference in minute ventilation related to difference in arterial oxygen saturation (delta V'E/ delta Sa,O2) (L.min-1/%) was significantly lower in subjects susceptible to HAPE (mean +/- SEM 0.8 +/- 0.1; n = 10) compared to nonsusceptible controls (1.5 +/- 0.2; n = 10), but was not significantly different from subjects susceptible to AMS (1.2 +/- 0.2; n = 10). Hypercapnic ventilatory response was not significantly different between the three groups. Discrimination between groups could not be improved by measurements of HVR during exercise (50% maximum oxygen consumption (V'O2,max)), or by assessing ventilation and oxygen saturation during a 15 min steady-state exercise (35% V'O2,max) at fractional inspiratory oxygen (FI,O2) of 0.14. Pulmonary artery pressure (Ppa) estimated by Doppler measurements of tricuspid valve pressure at an FI,O2 of 0.21 and 0.12 (10 min) did not lead to a further discrimination between subjects susceptible to HAPE and AMS with the exception of three subjects susceptible to HAPE who showed an exaggerated HPVR. It is concluded that a low ventilatory response to hypoxia is associated with an increased risk for high altitude pulmonary oedema, whilst susceptibility to acute mountain sickness may be associated with a high or low ventilatory response to hypoxia. A reliable discrimination between subjects susceptible to high altitude pulmonary oedema and acute mountain sickness with a low ventilatory response to hypoxia is not possible by Doppler echocardiographic estimations of hypoxic pulmonary vascular response.

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