RhEPO improves time to exhaustion by non-hematopoietic factors in humans

Abstract

Purpose: Erythropoietin (EPO) controls red cell volume (RCV) and plasma volume (PV). Therefore, injecting recombinant human EPO (rhEPO) increases RCV and most likely reduces PV. RhEPO-induced endurance improvements are explained by an increase in blood oxygen (O2) transport capacity, which increases maximum O2 uptake ((Formula presented.) O2max). However, it is debatable whether increased RCV or (Formula presented.) O2max are the main reasons for the prolongation of the time to exhaustion (tlim) at submaximal intensity. We hypothesized that high rhEPO doses in particular contracts PV such that the improvement in tlim is not as strong as at lower doses while (Formula presented.) O2max increases in a dose-dependent manner. Methods: We investigated the effects of different doses of rhEPO given during 4 weeks [placebo (P), low (L), medium (M), and high (H) dosage] on RCV, PV, (Formula presented.) O2max and tlim in 40 subjects. Results: While RCV increased in a dose-dependent manner, PV decreased independent of the rhEPO dose. The improvements in tlim (P +21.4 ± 23.8 %; L +16.7 ± 29.8 %; M +44.8 ± 62.7 %; H +69.7 ± 73.4 %) depended on the applied doses (R2 = 0.89) and clearly exceeded the dose-independent (Formula presented.) O2max increases (P −1.7 ± 3.2 %; L +2.6 ± 6.8 %; M +5.7 ± 5.1 %; H +5.6 ± 4.3 %) after 4 weeks of rhEPO administration. Furthermore, the absolute tlim was not related (R2 ≈ 0) to RCV or to (Formula presented.) O2max. Conclusions: We conclude that a contraction in PV does not negatively affect tlim and that rhEPO improves tlim by additional, non-hematopoietic factors.