Effects of erythropoietin administration on cerebral metabolism and exercise capacity in men.
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 + or - 7 kg) received either 3 days of high-dose (30,000 IU/day; n = 7) double-blinded 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 approximately 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.
Department of Anesthsia, Rishospitalet, Copenhagen.
P
P
Rasmussen
E M
EM
Foged
R
R
Krogh-Madsen
J
J
Nielsen
T R
TR
Nielsen
N V
NV
Olsen
N C
NC
Petersen
T A
TA
Sørensen
N H
NH
Secher
C
C
Lundby
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002560:Cerebrovascular Circulation; D003071:Cognition; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D017079:Exercise Tolerance / Q000187:drug effects*; D006397:Hematinics / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D019344:Lactic Acid / Q000097:blood; D008297:Male; D020768:Middle Cerebral Artery / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D010465:Perception; D015990:Placebo Effect; D012123:Pulmonary Ventilation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation; D017585:Ultrasonography, Doppler, Transcranial; D055815:Young Adult
D015415:Biomarkers; D001786:Blood Glucose; D006397:Hematinics; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D019344:Lactic Acid; D010100:Oxygen