Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport?

1 Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark; 2 Department of Sport Science, University of Århus, Århus, Denmark; 3 Ecole Nationale de Ski et d'Alpinisme, Chamonix, France; 4 Department of Exercise Science, Concordia University, Montreal, Quebec, Canada; 5 Copenhagen Muscle Research Centre, Department of Anaesthesia, Rigshospitalet, Copenhagen, Denmark; 6 School of Physical Education, Department of Sports Medicine and Exercise Science, University of Athens, Athens, Greece; and 7 Department of Physical Education, University of Las Palmas de Gran, Canaria, Spain Submitted 3 April 2008 ; accepted in final form 29 May 2008 This study was performed to test the hypothesis that administration of recombinant human erythropoietin (rHuEpo) in humans increases maximal oxygen consumption by augmenting the maximal oxygen carrying capacity of blood. Systemic and leg oxygen delivery and oxygen uptake were studied during exercise in eight subjects before and after 13 wk of rHuEpo treatment and after isovolemic hemodilution to the same hemoglobin concentration observed before the start of rHuEpo administration. At peak exercise, leg oxygen delivery was increased from 1,777.0 ± 102.0 ml/min before rHuEpo treatment to 2,079.8 ± 120.7 ml/min after treatment. After hemodilution, oxygen delivery was decreased to the pretreatment value (1,710.3 ± 138.1 ml/min). Fractional leg arterial oxygen extraction was unaffected at maximal exercise; hence, maximal leg oxygen uptake increased from 1,511.0 ± 130.1 ml/min before treatment to 1,793.0 ± 148.7 ml/min with rHuEpo and decreased after hemodilution to 1,428.0 ± 111.6 ml/min. Pulmonary oxygen uptake at peak exercise increased from 3,950.0 ± 160.7 before administration to 4,254.5 ± 178.4 ml/min with rHuEpo and decreased to 4,059.0 ± 161.1 ml/min with hemodilution ( P = 0.22, compared with values before rHuEpo treatment). Blood buffer capacity remained unaffected by rHuEpo treatment and hemodilution. The augmented hematocrit did not compromise peak cardiac output. In summary, in healthy humans, rHuEpo increases maximal oxygen consumption due to augmented systemic and muscular peak oxygen delivery. hemoglobin concentration Address for reprint requests and other correspondence: C. Lundby, Copenhagen Muscle Research Center, Rigshospitalet, section 7652, Blegdamsvej 9, 2100 Copenhagen, Denmark (e-mail: lundby{at}idraet.au.dk )