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J Physiol Volume 568, Number 2, 639-652, October 15, 2005 DOI: 10.1113/jphysiol.2005.089920
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Influence of recombinant human erythropoietin treatment on pulmonary O2 uptake kinetics during exercise in humans

Daryl P Wilkerson1, Jörn Rittweger1, Nicolas J. A Berger1, Patrick F Naish2 and Andrew M Jones1

1 Department of Exercise and Sport Science, Manchester Metropolitan University, Hassall Road, Alsager, ST7 2HL, UK
2 Directorate of Renal Medicine, North Staffordshire Hospital Trust, ST4 7LN, UK

We hypothesized that 4 weeks of recombinant human erythropoietin (RhEPO) treatment would result in a significant increase in haemoglobin concentration ([Hb]) and arterial blood O2-carrying capacity and that this would (1) increase peak pulmonary oxygen uptake {tjp_1147_mu1} during ramp incremental exercise, and (2) speed {tjp_1147_mu2} 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 {tjp_1147_mu3}, 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 {tjp_1147_mu4} (heavy), and 105% {tjp_1147_mu5} (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], {tjp_1147_mu6} 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 {tjp_1147_mu7} (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 {tjp_1147_mu8} 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 O2-carrying capacity and thus the potential for muscle O2 delivery with RhEPO treatment enhanced the peak {tjp_1147_mu9} but did not influence {tjp_1147_mu10} kinetics, suggesting that the latter is principally regulated by intracellular (metabolic) factors, even during exercise where the {tjp_1147_mu11} requirement is greater than the {tjp_1147_mu12}, at least in young subjects performing upright cycle exercise.

(Received 5 May 2005; accepted after revision 2 August 2005; first published online 4 August 2005)
Corresponding author A. M. Jones: School of Sport and Health Sciences, St. Luke's Campus, University of Exeter, Heavitree Road, Exeter, EX1 2LU.. Email: a.m.jones{at}exeter.ac.uk




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