title: Proposed mechanisms for the anabolic steroid-induced increase in myocardial susceptibility to ischaemia/reperfusion injury.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Medical Physiology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg.
authors.forename: E F
authors.initials: EF
authors.lastname: Du Toit
authors.forename: E
authors.initials: E
authors.lastname: Rossouw
authors.forename: J
authors.initials: J
authors.lastname: Van Rooyen
authors.forename: A
authors.initials: A
authors.lastname: Lochner
mesh_terms: D045930:Anabolic Agents / Q000009:adverse effects*; D000728:Androgens / Q000009:adverse effects*; D000818:Animals; D006152:Cyclic GMP / Q000032:analysis; D004198:Disease Susceptibility / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced*; D009206:Myocardium / Q000737:chemistry; D009277:Nandrolone / Q000009:adverse effects*; D009929:Organ Size; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D045930:Anabolic Agents; D000728:Androgens; D014409:Tumor Necrosis Factor-alpha; D009277:Nandrolone; D006152:Cyclic GMP