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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. lbrglIgHypothesis:l/Ig AAS use increases myocardial susceptibility to ischaemia / reperfusion injury. lbrglIgMethods:l/Ig 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 TNF<SPAN lang=AF style=FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol><SPAN style=mso-char-type: symbol; mso-symbol-font: Symbolgal/SPANgl/SPANg concentrations. lbrglIgResults:l/Ig Anabolic steroids decreased the rate pressure product (RPP) of the exercise-trained rat heart [34 582 lug+l/ug 1 778 mmHg/min vs 28 868 lug+l/ug 2 446 mmHg/min for exercise-trained steroid-treated hearts (lIgpl/Ig < 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 lug+l/ug 2 026 mmHg/min vs 12 018 lug+l/ug 1 725 mmHg/min for sedentary steroid-treated hearts and, 21 892 lug+l/ug 2 912 mmHg vs 12 838 lug+l/ug 1 536 mmHg/min for exercise-trained steroidtreated hearts). Myocardial TNF<SPAN lang=AF style=FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol><SPAN style=mso-char-type: symbol; mso-symbol-font: Symbolgal/SPANgl/SPANg [267.75 lug+l/ug 44.25 pg/g vs 190.00 lug+l/ug 15.75 pg/g (lIgpl/Ig < 0.05)] and cAMP concentrations [406.04 lug+l/ug 18.41 pmol/g vs 235.6 lug+l/ug 43.26 pmol/g (lIgpl/Ig < 0.05)] were elevated in the steroid-treated hearts when compared with their untreated counterparts. lbrglIgConclusions:l/Ig 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 TNF<SPAN lang=AF style=FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol><SPAN style=mso-char-type: symbol; mso-symbol-font: Symbolgal/SPANgl/SPANg concentrations.