Erythropoietin Promotes Deleterious Cardiovascular Effects and Mortality Risk in a Rat Model of Chronic Sports Doping
Athletes who abuse recombinant human erythropoietin (rhEPO) consider only the benefit to performance and usually ignore the potential short and long-term liabilities. Elevated haematocrit and dehydratation associated with intense exercise may reveal undetected cardiovascular risk, but the mechanisms underlying it remain to be fully explained. This study aimed to evaluate the cardiovascular effects of rhEPO in rats under chronic aerobic exercise. A ten week protocol was performed in four male Wistar rat groups: control—sedentary; rhEPO—50 IU kg−1, 3 times/wk; exercised (EX)—swimming for 1 h, 3 times/wk; EX + rhEPO. One rat of the EX + rhEPO group suffered a sudden death episode during the week 8. rhEPO in trained rats promoted erythrocyte count increase, hypertension, heart hypertrophy, sympathetic and serotonergic overactivation. The suddenly died rat’s tissues presented brain with vascular congestion; left ventricular hypertrophy, together with a “cardiac-liver”, suggesting the hypothesis of heart failure as cause of sudden death. In conclusion, rhEPO doping in rats under chronic exercise promotes not only the expected RBC count increment, suggesting hyperviscosity, but also other serious deleterious cardiovascular and thromboembolic modifications, including mortality risk, which might be known and assumed by all sports authorities, including athletes and their physicians.
KeywordsrhEPO Doping Chronic aerobic exercise Cardiovascular and mortality risk
We are very grateful to Roche Pharmaceuticals for providing the rhEPO used.
- 1.Lacombe, C., & Mayeux, P. (2006). Biology of erythropoietin. Haematologica, 83, 724–732.Google Scholar
- 5.Robinson, N., Mangin, P., & Saugy, M. (2003). Erythropoietin abuse in sports. Sysmex Journal International, 13, 75–77.Google Scholar
- 11.Reis, F., Rocha, L., Ponte, L., Alcobia, T., Almeida, L., Costa-Almeida, C., et al. (2005). Effect of preventive and regressive isosorbide 5-mononitrate treatment on catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in cyclosporin A-induced hypertensive rats. Life Science, 77, 2514–2528.CrossRefGoogle Scholar
- 12.Estepa, V., Ródenas, S., & Martín, M. C. (2001). Optimización de un método para la determinación de la peroxidación lipídica en suero humano. Anales de la Real Academia de Farmacia, 67, 1–17.Google Scholar
- 14.Cruz, A. (2006). Resistência aeróbia e eritropoietina. Goiânia, 33, 553–572.Google Scholar
- 15.Cazzola, M. (2002). A global strategy for prevention and detection of blood doping with erythropoietin and related drugs. Haematologica, 85, 561–563.Google Scholar
- 18.Gauthier, J. (2001). Effets cardiovasculaires du dopage. Annales de Cardiologie et d’Angeiologie, 50293, 8.Google Scholar
- 29.Manolis, A. S., Tzeism, S., Triantafyllou, K., Michaelidis, J., Pyrros, I., Sakellaris, N., et al. (2005). Erythropoietin in heart failure and other cardiovascular diseases: Hematopoietic and pleiotropic effects. Current Drug Targets—Cardiovascular and Haematological Disorders, 5, 355–375.CrossRefPubMedGoogle Scholar
- 30.Regidor, D. L., Kopple, J. D., Kovesdy, C. P., Kilpatrick, R. D., McAllister, C. J., Aronovitz, J., et al. (2006). Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients. Journal of the American Society of Nephrology, 17, 1181–1191.CrossRefPubMedGoogle Scholar