Influence of recombinant human erythropoietin treatment on pulmonary O2 uptake kinetics during exercise in humans

We hypothesized that 4 weeks of recombinant human erythropoietin (RhEPO) treatment would result in a significant increase in haernoglobin concentration ([Hb]) and arterial blood O-2-carrying capacity and that this would (1) increase peak pulmonary oxygen uptake (Vo(2),) during ramp incremental exercise, and (2) speed Vo(2), kinetics during 'severe'-, but not 'moderate' or 'heavy' -intensity, step exercise. Fifteen subjects (mean +/- S.D). age 25 +/- 4 years) were randomly assigned to either an experimental group which received a weekly subcutaneous injection of RhEPO 150 IU kg(-1); n = 8), or a control group (CON) which received a weekly subcutaneous injection of sterile saline (10 ml; n = 7) as a placebo, for four weeks. The subjects and the principal researchers were both blind with respect to the group assignment. Before and after the intervention period, all subjects completed a ramp test for determination of the gas exchange threshold (GET) and Vo(2),(peak), and a number of identical 'step' transitions from 'unloaded' cycling to work rates requiring 80% GET (moderate), 70% of the difference between the GET and Vo(2,peak) (heavy), and 105% Vo(2),(peak) (severe) as determined from the initial ramp test. Pulmonary gas exchange was measured breath-by-breath. There were no significant differences between the RhEPO and CON groups for any of the measurements of interest ([Hb],) Vo(2,peak), Vo(2) kinetics) before the intervention. Four weeks of RhEPO treatment resulted in a 7% increase both in [Hb] (from 15.8 +/- 1.0 to 16.9 +/- 0.7 g dl(-1); P < 0.01) and Vo(2,peak) (from 47.5 +/- 4.2 to 50.8 +/- 10.7 ml kg(-1).min(-1); P < 0.05), with no significant change in CON. RhEPO had no significant effect on Vo(2) kinetics for moderate (Phase II time constant, from 28 +/- 8 to 28 +/- 7 s), heavy (from 37 +/- 12 to 35 +/- 11 s), or severe (from 33 +/- 15 to 35 +/- 15 s) step exercise. Our results indicate that enhancing blood O-2-carrying capacity and thus the potential for muscle 02 delivery with RhEPO treatment enhanced the peak Vo(2), but did not influence Vo(2) kinetics, suggesting that the latter is principally regulated by intracellular (metabolic) factors, even during exercise where the Vo(2) requirement is greater than the Vo(2peak), at least in young subjects performing upright cycle exercise.