The ergogenic effect of recombinant human erythropoietin on VO2max depends on the severity of arterial hypoxemia.
Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood oxygen-carrying capacity (CaO(2)) that unequivocally enhances maximal oxygen uptake (VO(2)max) during exercise in normoxia, but not when exercise is carried out in severe acute hypoxia. This implies that there should be a threshold altitude at which VO(2)max is less dependent on CaO(2). To ascertain which are the mechanisms explaining the interactions between hypoxia, CaO(2) and VO(2)max we measured systemic and leg O(2) transport and utilization during incremental exercise to exhaustion in normoxia and with different degrees of acute hypoxia in eight rhEpo-treated subjects. Following prolonged rhEpo treatment, the gain in systemic VO(2)max observed in normoxia (6-7%) persisted during mild hypoxia (8% at inspired O(2) fraction (F(I)O(2)) of 0.173) and was even larger during moderate hypoxia (14-17% at F(I)O(2) = 0.153-0.134). When hypoxia was further augmented to F(I)O(2) = 0.115, there was no rhEpo-induced enhancement of systemic VO(2)max or peak leg VO(2). The mechanism highlighted by our data is that besides its strong influence on CaO(2), rhEpo was found to enhance leg VO(2)max in normoxia through a preferential redistribution of cardiac output toward the exercising legs, whereas this advantageous effect disappeared during severe hypoxia, leaving augmented CaO(2) alone insufficient for improving peak leg O(2) delivery and VO(2). Finally, that VO(2)max was largely dependent on CaO(2) during moderate hypoxia but became abruptly CaO(2)-independent by slightly increasing the severity of hypoxia could be an indirect evidence of the appearance of central fatigue.
Robach
Paul
P
Ecole Nationale de Ski et d'Alpinisme, Chamonix, France. paul.robach@jeunesse-sports.gouv.fr
Calbet
Jose A L
JA
Thomsen
Jonas J
JJ
Boushel
Robert
R
Mollard
Pascal
P
Rasmussen
Peter
P
Lundby
Carsten
C
D002302:Cardiac Output / Q000187:drug effects; D004334:Drug Administration Schedule; D004911:Erythrocyte Volume / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology*; D001239:Inhalation / Q000502:physiology; D007501:Iron / Q000494:pharmacology; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D010809:Physical Fitness; D011994:Recombinant Proteins; D012016:Reference Values
D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron