ToxSci Advance Access originally published online on July 25, 2007
Toxicological Sciences 2007 99(2):605-611; doi:10.1093/toxsci/kfm186
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Nandrolone Potentiates Arrhythmogenic Effects of Cardiac Ischemia in the Rat
* Department of Clinical & Experimental Pharmacology, University of Adelaide
CSIRO, Health Sciences & Nutrition, Kintore Avenue, Adelaide, SA 5000 Australia
Cardiology Unit, The Queen Elizabeth Hospital, Woodville 5011, Australia
2 To whom correspondence should be addressed at Department of Clinical & Experimental Pharmacology, L5 Medical School North, University of Adelaide, South Australia 5000, Australia. Fax: +61-8-8224-0685. E-mail: rod.irvine{at}adelaide.edu.au.
Received April 19, 2007; accepted June 25, 2007
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Abstract |
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Anabolic steroid abuse has been associated with thrombosis and arteriosclerosis, both of which predispose to myocardial ischemia and infarction. However, there are reports of sudden cardiac death in the absence of thrombus and atheroma following anabolic steroid use. Although treatment with the commonly abused steroid, nandrolone, has been shown to decrease recovery of systolic function following ischemia in isolated rat hearts, it is unknown whether anabolic steroids can increase the incidence of fatal arrhythmia associated with cardiac ischemia. Anesthetized male Sprague–Dawley rats were administered vehicle or nandrolone (10–160 µg/kg/min iv) 10 min prior to 15-min occlusion of the left anterior descending coronary artery followed by 10-min reperfusion. Nandrolone, in this dose range, did not significantly change heart rate, blood pressure, or cardiac rhythm in the absence of ischemia. However, the fraction of rats surviving ischemia was significantly (p < 0.05) decreased by nandrolone at both 40 and 160 µg/kg/min, while survival time during ischemia was decreased significantly (p < 0.001) by nandrolone 160 µg/kg/min. An increase (p < 0.05) in the duration of ventricular fibrillation was noted at the highest compared to the lowest dose of nandrolone, corresponding to a significant increase in the fraction of rats experiencing ventricular fibrillation (p < 0.01). Nandrolone had no effect on the frequency or duration of ventricular fibrillation or survival time during reperfusion. Although the mechanisms underlying these effects are currently unclear, they indicate that exposure to anabolic steroids in combination with transient reductions in coronary blood flow may explain some reports of sudden cardiac death in anabolic steroid users.
Key Words: nandrolone; cardiac; ischemia; arrhythmia; ventricular fibrillation.
1 Current address: Mayne Pharma International, 1538 Main North Road, Salisbury South, South Australia 5106.