The effects of 17 alpha-methyltestosterone on myocardial function in vitro

Testosterone analogs have been used as performance enhancers by athletes fo r more than 40 yr. We asked whether the anabolic steroid 17 alpha-methyl-4- androstene-17-ol-3-one (17 alpha-MT) would affect intrinsic contractile fun ction of the heart. Male Sprague-Dawley rats, 125-150 g, were treated with 17 alpha-MT either parenterally or orally for up to 8 wk. Intrinsic contrac tile function of the hearts was assessed utilizing both the isolated workin g heart and isovolumic perfused heart preparations. Isolated working hearts from 17 alpha-MT-treated rats had a 45% decrease in heart work attributabl e largely to a similarly decreased stroke volume. Isovolumic perfused heart s from treated animals had elevated left ventricular systolic and diastolic pressures at similar interventricular volumes compared to controls. Rates of ventricular pressure development (+dP/dT) or relaxation (-dP/dT) were un changed as a result of the treatment. However, static elastance was reduced in potassium-arrested hearts from the 17 alpha-MT treatment (63% increase in interventricular pressure), consistent with a limitation being imposed o n stroke volume by a decreased myocardial compliance. Hydroxyproline conten t of the hearts was not altered by 17 alpha-MT treatment suggesting that in creased stiffness was not a consequence of collagen proliferation. Treatmen t of the steroid rats with beta-aminopropionitrile, a compound that inhibit s lysyl oxidase, restored the left ventricular volume-pressure relationship (elastance curve) to that of control hearts. Thus, chronic treatment with anabolic steroids appears to reduce left ventricular compliance, possibly r elated to an enhanced activity of lysyl oxidase, and results in increased c rosslink formation between collagen strands in the extracellular matrix.