Poster Presenter

Cardiac Lesions Induced by Testosterone: Protective Effects of Dexrazoxane and Trimetazidine
Timour Q, Belhani D, Fanton L, Tabib A
France

Sudden death of cardiac origin is frequently observed in athletes with a history of illicit products abuse to increase physical performance. Anabolic steroids play a significant role amongst these substances. The aim of this work was: 1) to precisely describe the nature of heart lesions resulting from anabolic steroid abuse in athletes who suddenly died, and in rabbits treated with norethandrolone (NED) or testosterone (TST); 2) to elucidate the underlying mechanism(s) and finally; 3) to test whether anti-ischemia (trimetazidine: TMZ) or cardioprotective (dexrazoxane: DEX) drugs could protect the heart from anabolic steroids and prevent the development of lesions.

The human component of these investigations was performed in the Forensic Medicine Institute of Lyon (IML) from judicial necropsies on persons deceased from sudden death between 1981 and 2004. During this period, 15,000 necropsies have been performed in IML and 1,800 had evidence of cardiac lesions. Among these 1,800 deaths, 120 had occurred during recreational (108 deaths, i.e. 90%) or professional (12 deaths, i.e. 10%) sport. In the latter group, post-mortem findings evidenced that among the 12 athletes who suddenly died, 6 had acute aggravation of a pre-existing common cardiopathy (cardiac hypertrophy, dilated cardiopathy, right ventricle arrythmogenic cardiopathy.) and 6 had various lesions such as toxic (disorganized architecture, necrosis, lymphocytic infiltrates.) or acute and chronic myocardiopathy (endocardial and interstitial fibrosis, distal vascular lesions) due to the abuse of doping substances.

The experimental component of these investigations was conducted in 36 New Zealand rabbits of both sexes, weighting 2.5 kg at the start of the study, and included in 2 different studies. In study 1, 6 rabbits were treated orally with saline (GI) and 6 with 8 mg/kg/d of NED (GII). In study 2, groups of 6 rabbits were treated intraperitoneally with saline (GIII), 8 mg/kg/d of TST (GIV), 8 mg/kg/d of TST combined with 5 mg/kg/d of TMZ ( GV), or 8 mg /kg/d or TST combined with 60 mg/kg/d of DEX (GVI). The animals were treated for 60 days and maintained in the laboratory's animal facilities until day 90 for scheduled necropsy with pentobarbital (88 mg/kg intravenously). The hearts were immediately removed, weight and cut into two parts: the distal part was used for the histopathological examination and the proximal part for the measurement of apoptosis.

The histopathological examination showed marked cardiac lesions (dysmorphic myocyte nuclei, disorganized myocardial fibers, myolysis, dysplasia of the intra-myocardial arteriolar network, fibrosis with lymphocytic infiltrates and necrosis) in the animals treated with NED or TST. Apoptosis measured from caspase-3 activity was significantly increased in NED-treated animals as compared to controls. In contrast, no cardiac lesions were observed in control animals as well as animals treated with TST when combined with either TMZ or DEX.