High-altitude physiology: lessons from Tibet

Abstract

Polycythemia is a universal lowlander response to altitude; healthy Andean high-altitude natives also have elevated [Hb]. While this may enhance O₂ transport to tissues, studies have shown that acute isovolumic changes in [Hb] do not affect exercise capacity. Many high-altitude Tibetans have evolved sea-level values of [Hb], providing a natural opportunity to study this issue. In 21 young healthy male Tibetans with [Hb] between 15 and 23 g/dl, we measured VO₂MAX and O₂ transport capacity at 4200m. VO₂MAX was higher when [Hb] was lower (P<0.05), enabled by both higher cardiac output and muscle O₂ diffusional conductance, but neither ventilation nor the alveolar-arterial PO₂ difference (AaPO₂) varied with [Hb]. In contrast, Andean high altitude natives remain polycythemic with larger lungs and higher lung diffusing capacity, a smaller exercising AaPO₂, and lower ventilation. The challenges now are (1) to understand the different adaptive pathways used by Andeans and Tibetans, and (2) to determine in Tibetans whether, during evolution, reduced [Hb] appeared first, causing compensatory cardiac and muscle adaptations, or if enhanced cardiac function and muscle O₂ transport capacity appeared first, permitting secondary reduction in [Hb]. For (2), further research is necessary to determine the basis of enhanced cardiac function and muscle O₂ transport, and identify molecular targets of evolution in heart and muscle. Putative mutations can then be timed and compared to appearance of those affecting [Hb].