The Ergogenic Effect of Recombinant Human Erythropoietin on V̇O2max Depends on the Severity of Arterial Hypoxemia

Abstract

Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood oxygen-carrying capacity (CaO2) that unequivocally enhances maximal oxygen uptake (V̇O2max) during exercise in normoxia, but not when exercise is carried out in severe acute hypoxia. This implies that there should be a threshold altitude at which V̇O2max is less dependent on CaO2. To ascertain which are the mechanisms explaining the interactions between hypoxia, CaO2 and V̇O2max we measured systemic and leg O2 transport and utilization during incremental exercise to exhaustion in normoxia and with different degrees of acute hypoxia in eight rhEpo-treated subjects. Following prolonged rhEpo treatment, the gain in systemic V̇O2max observed in normoxia (6–7%) persisted during mild hypoxia (8% at inspired O2 fraction (FIO2) of 0.173) and was even larger during moderate hypoxia (14–17% at FIO2 = 0.153–0.134). When hypoxia was further augmented to FIO2 = 0.115, there was no rhEpo-induced enhancement of systemic V̇O2max or peak leg V̇O2. The mechanism highlighted by our data is that besides its strong influence on CaO2, rhEpo was found to enhance leg V̇O2max in normoxia through a preferential redistribution of cardiac output toward the exercising legs, whereas this advantageous effect disappeared during severe hypoxia, leaving augmented CaO2 alone insufficient for improving peak leg O2 delivery and V̇O2. Finally, that V̇O2max was largely dependent on CaO2 during moderate hypoxia but became abruptly CaO2-independent by slightly increasing the severity of hypoxia could be an indirect evidence of the appearance of central fatigue