Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men

TY - JOUR

T1 - Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men

AU - Rasmussen, Peter

AU - Foged, Eva M

AU - Krogh-Madsen, Rikke

AU - Nielsen, Jannie

AU - Nielsen, Thomas R

AU - Olsen, Niels Vidiendal

AU - Petersen, Nicolas C

AU - Sørensen, Thomas A

AU - Secher, Niels H

AU - Lundby, Carsten

AU - Rasmussen, P

AU - Foged, E. M.

AU - Krogh-Madsen, R

AU - Nielsen, J

AU - Nielsen, T. Rune

AU - Olsen, N V

AU - Petersen, N C

AU - Sørensen, T A

AU - Secher, N H

AU - Lundby, Carsten

N1 - CURIS 2010 5200 096

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Recombinant human erythropoietin (EPO) increases exercise capacity by stimulating erythropoiesis and subsequently enhancing oxygen delivery to the working muscles. In a large dose, EPO crosses the BBB and may reduce central fatigue and improve cognition. In turn, this would augment exercise capacity independent of erythropoiesis. To test this hypothesis, 15 healthy young men (18-34 years old, 74 ± 7 kg) received either 3 days of high-dose (30,000 IU/day; n = 7) doubleblinded placebo controlled or 3 mo of low-dose (5,000 IU/wk; n = 8) counter-balanced open but controlled administration of EPO. We recorded exercise capacity, transcranial ultrasonography-derived middle cerebral artery blood velocity, and arterial-internal jugular venous concentration differences of glucose and lactate. In addition, cognitive function, ratings of perceived exertion, ventilation, and voluntary activation by transcranial magnetic stimulation-induced twitch force were evaluated. Although EPO in a high dose increased cerebrospinal fluid EPO concentration ∼20-fold and affected ventilation and cerebral glucose and lactate metabolism (P < 0.05), 3 days of high-dose EPO administration had no effect on cognition, voluntary activation, or exercise capacity, but ratings of perceived exertion increased (P < 0.05). We confirmed that 3 mo of administration of EPO increases exercise capacity, but the improvement could not be accounted for by other mechanisms than enhanced oxygen delivery. In conclusion, EPO does not attenuate central fatigue or change cognitive performance strategy, suggesting that EPO enhances exercise capacity exclusively by increased oxygen delivery to the working muscles.

AB - Recombinant human erythropoietin (EPO) increases exercise capacity by stimulating erythropoiesis and subsequently enhancing oxygen delivery to the working muscles. In a large dose, EPO crosses the BBB and may reduce central fatigue and improve cognition. In turn, this would augment exercise capacity independent of erythropoiesis. To test this hypothesis, 15 healthy young men (18-34 years old, 74 ± 7 kg) received either 3 days of high-dose (30,000 IU/day; n = 7) doubleblinded placebo controlled or 3 mo of low-dose (5,000 IU/wk; n = 8) counter-balanced open but controlled administration of EPO. We recorded exercise capacity, transcranial ultrasonography-derived middle cerebral artery blood velocity, and arterial-internal jugular venous concentration differences of glucose and lactate. In addition, cognitive function, ratings of perceived exertion, ventilation, and voluntary activation by transcranial magnetic stimulation-induced twitch force were evaluated. Although EPO in a high dose increased cerebrospinal fluid EPO concentration ∼20-fold and affected ventilation and cerebral glucose and lactate metabolism (P < 0.05), 3 days of high-dose EPO administration had no effect on cognition, voluntary activation, or exercise capacity, but ratings of perceived exertion increased (P < 0.05). We confirmed that 3 mo of administration of EPO increases exercise capacity, but the improvement could not be accounted for by other mechanisms than enhanced oxygen delivery. In conclusion, EPO does not attenuate central fatigue or change cognitive performance strategy, suggesting that EPO enhances exercise capacity exclusively by increased oxygen delivery to the working muscles.

U2 - 10.1152/japplphysiol.00234.2010

DO - 10.1152/japplphysiol.00234.2010

M3 - Journal article

SN - 8750-7587

VL - 109

SP - 476

EP - 483

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

IS - 2

ER -