Sea-level haemoglobin concentration is associated with greater exercise capacity in Tibetan males at 4200 m.

NEW FINDINGS: What is the topic of this review? Recent developments link relatively lower hemoglobin concentration in Tibetans at high altitude to exercise capacity and components of oxygen transport. What advances does it highlight? Haemoglobin concentration (ranging from 15.2 to 22.9 g dl(-1) ) in Tibetan males was negatively associated with peak oxygen (O2 ) uptake per kilogram, cardiac output and muscle O2 diffusion conductance. Most variance in the peak O2 uptake per kilogram of Tibetan males was attributed to cardiac output, muscle diffusional conductance and arterial partial pressure of CO2 . The mechanisms underlying these differences in oxygen transport in Tibetans require additional analyses. Despite residence at >4000 m above sea level, many Tibetan highlanders, unlike Andean counterparts and lowlanders at altitude, exhibit haemoglobin concentration ([Hb]) within the typical sea-level range. Genetic adaptations in Tibetans are associated with this relatively low [Hb], yet the functional relevance of the lower [Hb] remains unknown. To address this, we examined each major step of the oxygen transport cascade [ventilation (VE), cardiac output (QT) and diffusional conductance in lung (DL) and muscle (DM)] in Tibetan males at maximal exercise on a cycle ergometer. Ranging from 15.2 to 22.9 g dl(-1) , [Hb] was negatively associated with peak O2 uptake per kilogram (r = -0.45, P < 0.05) and both cardiac output (QT/kg: r = -0.54, P < 0.02) and muscle O2 diffusion conductance (DM/kg: r = -0.44, P < 0.05) but not ventilation, arterial partial pressure of O2 or pulmonary diffusing capacity. Most variance in peak O2 uptake per kilogram was attributed to QT, DM and arterial partial pressure of CO2 (r(2)  = 0.90). In summary, lack of polycythaemia in Tibetans is associated with increased exercise capacity, which is explained by elevated cardiac, muscle and, to a small extent, ventilatory responses rather than pulmonary gas exchange. Whether lower [Hb] is the cause or result of these changes in O2 transport or is causally unrelated will require additional study.

Low haemoglobin concentration in Tibetan males is associated with greater high-altitude exercise capacity.

Tibetans living at high altitude have adapted genetically such that many display a low erythropoietic response, resulting in near sea-level haemoglobin (Hb) concentration. We hypothesized that absence of the erythropoietic response would be associated with greater exercise capacity compared to those with high [Hb] as a result of beneficial changes in oxygen transport. We measured, in 21 Tibetan males with [Hb] ranging from 15.2 g dl(-1) to 22.9 g dl(-1) (9.4 mmol l(-1) to 14.2 mmol l(-1) ), [Hb], ventilation, volumes of O2 and CO2 utilized at peak exercise (V̇O2 and V̇CO2), heart rate, cardiac output and arterial blood gas variables at peak exercise on a cycle ergometer at ∼4200 m. Lung and muscle O2 diffusional conductances were computed from these measurements. [Hb] was related (negatively) to V̇O2 kg(-1) (r = -0.45, P< 0.05), cardiac output kg(-1) (QT kg(-1) , r = -0.54, P < 0.02), and O2 diffusion capacity in muscle (DM kg(-1) , r = -0.44, P<0.05), but was unrelated to ventilation, arterial partial pressure of O2 (PaO2) or pulmonary diffusing capacity. Using multiple linear regression, variance in peak V̇O2 kg(-1) was primarily attributed to QT, DM, and PCO2 (R(2) = 0.88). However, variance in pulmonary gas exchange played essentially no role in determining peak V̇O2. These results (1) show higher exercise capacity in Tibetans without the erythropoietic response, supported mostly by cardiac and muscle O2 transport capacity and ventilation rather than pulmonary adaptations, and (2) support the emerging hypothesis that the polycythaemia of altitude, normally a beneficial response to low cellular PO2, may become maladaptive if excessively elevated under chronic hypoxia. The cause and effect relationships among [Hb], QT, DM, and PCO2 remain to be elucidated.

Increased blood-oxygen binding affinity in Tibetan and Han Chinese residents at 4200 m.

High-altitude natives are challenged by hypoxia, and a potential compensatory mechanism could be reduced blood oxygen-binding affinity (P50), as seen in several high-altitude mammalian species. In 21 Qinghai Tibetan and nine Han Chinese men, all resident at 4200 m, standard P50 was calculated from measurements of arterial PO2 and forehead oximeter oxygen saturation, which was validated in a separate examination of 13 healthy subjects residing at sea level. In both Tibetans and Han Chinese, standard P50 was 24.5 ± 1.4 and 24.5 ± 2.0 mmHg, respectively, and was lower than in the sea-level subjects (26.2 ± 0.6 mmHg, P < 0.01). There was no relationship between P50 and haemoglobin concentration (the latter ranging from 15.2 to 22.9 g dl(-1) in Tibetans). During peak exercise, P50 was not associated with alveolar-arterial PO2 difference or peak O2 uptake per kilogram. There appears to be no apparent benefit of a lower P50 in this adult high-altitude Tibetan population.