CARDIOVASCULAR JOURNAL OF SOUTH AFRICA Vol 16, No. 1, January/February 2005 21 Summary Androgenic anabolic steroids (AAS) are often used by athletes to enhance athletic performance but are strong- ly associated with detrimental cardiovascular effects including sudden cardiac death. Hypothesis: AAS use increases myocardial susceptibility to ischaemia/reperfusion injury. Methods: Rats were trained (swimming) with or without intramuscular injection of nandrolone laurate (0.375 mg/kg). Untrained rats with or without nandrolone served as controls. Hearts were mounted on the Langendorff perfusion apparatus and mechanical function was mea- sured before and after 20-min normothermic global ischaemia. Myocardial tissue samples were collected for determination of tissue cyclic nucleotide and TNFα concentrations. Results: Anabolic steroids decreased the rate pressure product (RPP) of the exercise-trained rat heart [34 582 ± 1 778 mmHg/min vs 28 868 ± 2 446 mmHg/min for exercise-trained steroid-treated hearts (p < 0.05)]. Reperfusion RPP was lower in both the sedentary, and the exercise-trained, steroid-treated hearts than in their concurrent vehicle-treated controls (18 276 ± 2 026 mmHg/min vs 12 018 ± 1 725 mmHg/min for sedentary steroid-treated hearts and, 21 892 ± 2 912 mmHg vs 12 838 ± 1 536 mmHg/min for exercise-trained steroid- treated hearts). Myocardial TNFα [267.75 ± 44.25 pg/g vs 190.00 ± 15.75 pg/g (p < 0.05)] and cAMP concentra- tions [406.04 ± 18.41 pmol/g vs 235.6 ± 43.26 pmol/g (p < 0.05)] were elevated in the steroid-treated hearts when compared with their untreated counterparts. Conclusions: Supraphysiological doses of anabolic ste- roids, whether taken during exercise training or under sedentary conditions increase myocardial susceptibility to ischaemia/reperfusion injury in our model. This increased susceptibility may be related to steroid-induced increases in the pre-ischaemic myocardial cAMP con- centrations and/or increases in both pre-ischaemic and reperfusion TNFα concentrations. Cardiovasc J South Afr 2005; 16: 21–28. www.cvjsa.co.za Non-therapeutic use of androgenic anabolic steroids is prevalent among young, competitive male and female high school athletes who hope to improve their exercise perform- ance with these compounds. 1 They are administered in supraphysiological doses to enhance the development of muscle mass and strength and to reduce the recovery time after strenuous training bouts. 2,3 These doses are however associated with pathologic changes in numerous physiologi- cal systems. Studies using rats have shown that supra- physiological doses of anabolic steroids cause pathophysi- ological myocardial hypertrophy in this model. 3 In the mouse it has been associated with inadequate vascularisa- tion of the hypertrophied myocardium, 4 and in isolated rat ventricular myocytes it has been linked to increased apoptosis. 5 When combined with exercise, anabolic steroid use has been shown to change exercise-induced physi- ological cardiac hypertrophy to pathophysiological cardiac hypertrophy. 3 In this study using the exercising rat, the anabolic steroid-induced changes in myocardial hypertrophy were associated with changes in the ratio of the left ventricular wall thickness to internal radius. These changes are thought to lead to detrimental increases in LV wall stress and to act as one of the stimuli for abnormal heart growth and development. The exact mediators of myocardial hypertrophy are diverse and vary from mechanical stimuli to circulating humoral factors released by the heart and peripheral organs. Exercise-induced cardiac hypertrophy is thought to be due Cardiovascular Topics Department of Medical Physiology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg E.F. DU TOIT, Ph.D. E. ROSSOUW, M.Sc. A. LOCHNER, Ph.D. Department of Physiological Sciences, Faculty of Science, University of Stellenbosch, Stellenbosch J. VAN ROOYEN, Ph.D. Proposed mechanisms for the anabolic steroid-induced increase in myocardial susceptibility to ischaemia/reperfusion injury E.F. DU TOIT, E. ROSSOUW, J. VAN ROOYEN, A. LOCHNER