Proposed mechanisms for the anabolic steroid-induced increase in myocardial susceptibility to ischaemia/reperfusion injury.

UNLABELLED Androgenic anabolic steroids (AAS) are often used by athletes to enhance athletic performance but are strongly 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 measured before and after 20-min normothermic global ischaemia. Myocardial tissue samples were collected for determination of tissue cyclic nucleotide and TNFalpha 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 TNFalpha [267.75 +/- 44.25 pg/g vs 190.00 +/- 15.75 pg/g (p < 0.05)] and cAMP concentrations [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 steroids, 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 concentrations and/or increases in both pre-ischaemic and reperfusion TNFalpha concentrations.