Preserved peak exercise capacity in Andean highlanders with excessive erythrocytosis both before and after isovolumic hemodilution

In chronic mountain sickness (CMS), increased blood oxygen (O(2))-carrying capacity due to excessive erythrocytosis (EE, [Hb] ≥ 21 g/dL) could be offset, especially during exercise by both impaired cardiac output (Q̇t) and O(2) diffusion limitation in lungs and muscle. We hypothesized that EE results in reduced peak V̇o(2) despite increased blood O(2)-carrying capacity, and that isovolumic hemodilution (IVHD) improves exercise capacity. In 14 male residents of Cerro de Pasco, Peru (4,340 m), six with and eight without EE, we measured peak cycle-exercise capacity, V̇o(2), Q̇t, arterial blood gas parameters, and (resting) blood volume. This was repeated for participants with EE after IVHD, reducing hematocrit by 20% (from 67% to 53%). From these data, we quantified the major O(2) transport pathway components (ventilation, pulmonary alveolar-capillary diffusion, Q̇t, and blood-muscle mitochondria diffusion). Participants with EE had similar peak V̇o(2), systemic O(2) delivery, and O(2) extraction as non-EE controls, however, with lower Q̇t and higher arterial [O(2)]. After IVHD, peak V̇o(2) was preserved (but not enhanced), with lower O(2) delivery (despite higher Q̇t) balanced by greater O(2) extraction. The considerable variance in exercise capacity across the 14 individuals was explained essentially completely by differences in both pulmonary and muscle O(2) diffusional conductances and not by any differences in ventilation, [Hb], nor Q̇t. In conclusion, EE does not result in lower peak V̇o(2) in Andean males, and IVHD maintains, but does not enhance, exercise capacity. NEW & NOTEWORTHY Male Andean highlanders with and without excessive erythrocytosis (EE) have similar peak V̇o(2) at 4,340 m, with higher arterial [O(2)] in EE and lower cardiac output (Q̇t), thus maintaining similar O(2) delivery. Peak V̇o(2) in participants with EE was unaffected by isovolumic hemodilution (hematocrit reduced from 67% to 53%), with lower O(2) delivery balanced by slightly increased Q̇t and greater O(2) extraction. Differences in lung and muscle diffusing capacity, and not hematocrit variation, accounted for essentially all interindividual variance in peak V̇o(2).