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This version published online on July 10, 2003
Endocrinology, doi:10.1210/en.2003-0058
A more recent version of this article appeared on October 1, 2003
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Submitted on January 13, 2003
Accepted on July 1, 2003

Administration of testosterone is associated with a reduced susceptibility to myocardial ischemia

Frank Callies1*, Hinrik Strömer1, Robert H.G. Schwinger1, Birgit Bölck1, Kai Hu1, Stefan Frantz1, Andrea Leupold1, Stephanie Beer1, Bruno Allolio1, and Andreas W. Bonz1

1 Department of Endocrinology, Medical University Hospital Wuerzburg, Department of Cardiology, Medical University Hospital Wuerzburg; Clinic III for Internal Medicine, Laboratory of Muscle Physiology and Molecular Cardiology, University of Cologne

* To whom correspondence should be addressed. E-mail: Callies F{at}klinik.uni-wuerzburg.de.

This study investigated the impact of testosterone on myocardial ischemia-reperfusion injury and corresponding intracellular calcium metabolism ([Ca2+]i). Non-orchiectomized mature male Wistar rats were randomly assigned to either placebo, a single dose of testosterone undecanoate, or 5{alpha} -dihydrotestosterone. In a further series, orchiectomized rats were treated with placebo.

After two weeks of treatment the hearts were removed and placed in a Langendorff - setup. The isolated, buffer-perfused hearts were subjected to 30 min of no-flow ischemia and 30 min of reperfusion. Recovery of myocardial function was measured by analyzing pre- and postischemic left ventricular systolic / diastolic pressure and coronary perfusion pressure, simultaneously together with intracellular calcium handling (aequorin luminescence). Calcium regulatory proteins were analyzed by western blotting.

Left ventricular weight / bodyweight ratio was increased after administration of testosterone vs. orchectomized rats. The recovery of contractile function was improved in testosterone treated rats: at the end of the reperfusion left ventriclar systolic pressure was higher and enddiastolic pressure was lower in testosterone treated rats. End-ischemic [Ca2+]i and [Ca2+]i overload upon reperfusion was significantly lower in testosterone vs. orchiectomized rats too. Hovever, levels of calcium regulatory proteins remained unaffected.

In conclusion, administration of testosterone significantly improves recovery from global ischemia. These beneficial effects are associated with an attenuation of reperfusion induced [Ca2+]i overload.
Key words: myocardial function • reperfusion • testosterone • calcium • ischemia




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