Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport?
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.
Copenhagen Muscle Research Center, Department of Anaesthesia, Rigshospitalet, section 7652, Blegdamsvej 9, 2100 Copenhagen, Denmark. lundby@idraet.au.dk
C
C
Lundby
P
P
Robach
R
R
Boushel
J J
JJ
Thomsen
P
P
Rasmussen
M
M
Koskolou
J A L
JA
Calbet
D000328:Adult; D001693:Biological Transport, Active / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D004562:Electrocardiography / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D015444:Exercise / Q000502:physiology*; D006438:Hemodilution; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D011994:Recombinant Proteins; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012146:Rest / Q000502:physiology; D016683:Supine Position
D001786:Blood Glucose; D011994:Recombinant Proteins; D004921:Erythropoietin; D019344:Lactic Acid; D010100:Oxygen; D009638:Norepinephrine