title: RhEPO improves time to exhaustion by non-hematopoietic factors in humans.
abstract: OBJECTIVE
  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: see text]O2max). However, it is debatable whether increased RCV or [Formula: see text]O2max are the main reasons for the prolongation of the time to exhaustion (t lim) at submaximal intensity. We hypothesized that high rhEPO doses in particular contracts PV such that the improvement in t lim is not as strong as at lower doses while [Formula: see text]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: see text]O2max and t lim in 40 subjects.
  
  
  RESULTS
  While RCV increased in a dose-dependent manner, PV decreased independent of the rhEPO dose. The improvements in t lim (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 (R (2) = 0.89) and clearly exceeded the dose-independent [Formula: see text]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 t lim was not related (R (2) ≈ 0) to RCV or to [Formula: see text]O2max.
  
  
  CONCLUSIONS
  We conclude that a contraction in PV does not negatively affect t lim and that rhEPO improves t lim by additional, non-hematopoietic factors.
authors.affiliation: Exercise Physiology, Institute of Human Movement Sciences, ETH Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.|Laboratory for Protection and Physiology, EMPA, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014, St. Gallen, Switzerland.|Exercise Physiology, Institute of Physiology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Annaheim
authors.affiliation: Department of Anaesthesiology, University Hospital, Nussbaumstrasse 20, 80336, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Jacob
authors.affiliation: Division of Obstetrics, Department of Obstetrics and Gynaecology, University Hospital, 8000, Zurich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Krafft
authors.affiliation: Division of Obstetrics, Department of Obstetrics and Gynaecology, University Hospital, 8000, Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Breymann
authors.affiliation: Department of Anaesthesiology, University Hospital, Nussbaumstrasse 20, 80336, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Rehm
authors.affiliation: Exercise Physiology, Institute of Human Movement Sciences, ETH Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. urs.boutellier@hest.ethz.ch.|Exercise Physiology, Institute of Physiology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. urs.boutellier@hest.ethz.ch.|Exercise Physiology, ETH Zurich, Rychenbergstr. 49a, 8400, Winterthur, Switzerland. urs.boutellier@hest.ethz.ch.
authors.forename: Urs
authors.initials: U
authors.lastname: Boutellier
mesh_terms: D000328:Adult; D004911:Erythrocyte Volume / Q000187:drug effects*; D004921:Erythropoietin / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology*; D017079:Exercise Tolerance / Q000187:drug effects*; D006801:Humans; D008297:Male; D010101:Oxygen Consumption; D010953:Plasma Volume / Q000187:drug effects*; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin
keywords: Oxygen transport capacity; Plasma volume; Red blood cell volume; rhEPO doping