Cardiometabolic injury due to recombinant human erythropoietin doping for improvement of sports performance: chronic (training) versus acute (extenuating) aerobic exercise

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 chapter intended to compare the cardiometabolic effects of rhEPO treatment on rats under chronic vs acute extenuating exercise. The following male Wistar rat groups were assessed: control - sedentary (Sed); rhEPO - 50 IU/Kg/wk; Exercise (Ex) - swimming: 1 hr, 3 times/wk; Ex+rhEPO. For the chronic exercise a period of 10 wks was assessed, while for the acute exercise, a single bout of extenuating swimming was performed, with a rhEPO treatment for 3 wks prior to the acute section. Blood pressure and heart trophism were analysed. Blood and tissue samples were assessed for: biochemical data, haematology, catecholamine and serotoninergic measures, redox status and heart gene expression profile. The chronic Ex+rhEPO rats showed higher values of RBC, Htc and Hb vs chronic Ex, as well as vs acute Ex+rhEPO. Both chronic and acute swimming showed a remarkable sympathetic and serotonergic activation. rhEPO treatment in chronic training has promoted oxidative stress, in contrast with the antioxidant effect on the acute exercise. rhEPO in trained rats promoted erythrocyte count increase, hypertension, heart hypertrophy, sympathetic and serotonergic overactivation. One rat of the chronic Ex+rhEPO group suffered a sudden death episode during the week 8 and the tissues analyzed showed: brain with vascular congestion; left ventricular hypertrophy, together with a "cardiac liver", suggesting the hypothesis of heart failure as cause of sudden death. In the chronically trained rats, rhEPO per se promoted apoptosis, proliferation and angiogenesis, which was partially or totally prevented in the Ex+rhEPO rats. In conclusion, the effects of rhEPO doping in rats under exercise is notoriously more deleterious in circumstances that mimic high-performance athletes (chronic training) than in occasional consumers (acute sessions), particular due to increased cardiovascular risk. Chronic 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.