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Medicine & Science in Sports & Exercise:
CLINICAL SCIENCES: Clinically Relevant

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

LeGROS, TRACEY; McCONNELL, DOUGLAS; MURRY, TODD; EDAVETTAL, MATHEW; RACEY-BURNS, LOUISE A.; SHEPHERD, RAYMOND E.; BURNS, ALASTAIR H.

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Abstract

LeGROS, T., D. McCONNELL, T. MURRY, M. EDAVETTAL, L. A. RACEY-BURNS, R. E. SHEPHERD, and A. H. BURNS. The effects of 17α-methyltestosterone on myocardial function in vitro. Med. Sci. Sports Exerc., Vol. 32, No. 5, pp. 897–903, 2000. Testosterone analogs have been used as performance enhancers by athletes for more than 40 yr. We asked whether the anabolic steroid 17α-methyl-4-androstene-17-ol-3-one (17α-MT) would affect intrinsic contractile function of the heart. Male Sprague-Dawley rats, 125–150 g, were treated with 17α-MT either parenterally or orally for up to 8 wk. Intrinsic contractile function of the hearts was assessed utilizing both the isolated working heart and isovolumic perfused heart preparations. Isolated working hearts from 17α-MT-treated rats had a 45% decrease in heart work attributable largely to a similarly decreased stroke volume. Isovolumic perfused hearts 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 unchanged as a result of the treatment. However, static elastance was reduced in potassium-arrested hearts from the 17α-MT treatment (63% increase in interventricular pressure), consistent with a limitation being imposed on stroke volume by a decreased myocardial compliance. Hydroxyproline content of the hearts was not altered by 17α-MT treatment suggesting that increased stiffness was not a consequence of collagen proliferation. Treatment of the steroid rats with β-aminopropionitrile, a compound that inhibits 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 related to an enhanced activity of lysyl oxidase, and results in increased crosslink formation between collagen strands in the extracellular matrix.

Throughout history athletes have sought to enhance performance through the use of a variety of chemical substances. Over the last 4 decades the most widely used substances utilized for this purpose have been anabolic-androgenic steroids; derivatives or analogs of testosterone. The ability of these compounds to increase muscle mass and decrease body fat is well established (2). The abuse of these compounds now reaches to every level of competition from high school to international sports to professional athletes. Current legal statues classify anabolic steroids as controlled substances similar to opiates and barbiturates (13). Recent data also implicates a spreading of the usage of testosterone analogs to female high school athletes. It is estimated that 250,000 high school students may use these compounds as performance enhancers (23).

Anabolic steroids are known to induce a variety of alterations in hemodynamics and myocardial function. These include hypertension, hypo-α-lipoproteinemia, ultrastructural morphological changes, and alterations in left ventricular diastolic dimensions (1,6,8,9,20,21,25). Investigations into anabolic steroid induced alterations in cardiac function have produced inconsistent results. These appear to be due to differences in the specific steroid used, the dose, and the route by which it was administered. Ramo (21) reported that administration of methandienone (1.5 mg·kg1·d1 for 6 wk) decreased inotropic and chronotropic responses of the canine left ventricle in situ. Extending these studies to endurance trained animals, Ramo (21) demonstrated that steroid administration attenuated the exercise induced increase in left ventricular stroke work and the decrease in resting systemic vascular resistance). By contrast, Liang et al. 12) could find no significant differences in cardiac function between exercised rats and rats treated with nandrolone (3 mg·kg1·bw1 for 10 wk).

We designed experiments to determine the effects of chronic administration of 17α-methyl-4-androstene-17β-ol-3-one (17αMT) on intrinsic myocardial performance using isolated perfused hearts. This steroid was chosen because of the high incidence of its illicit use (4). The laboratory rat was chosen as an experimental animal because in the absence of cholesterol feeding atherogenesis does not occur in this animal model (5). This effectively eliminated influences of 17αMT on atherogenesis-mediated myocardial effects, thus allowing the more direct effects of the drug on myocardial function to be determined. When the initial experiments demonstrated significant changes in myocardial pumping capacity, several additional experiments were performed. Finally, experiments were designed to determine whether the inhibition of lysyl oxidase, the enzyme responsible for the construction of the cross links between adjacent strands of collagen, might attenuate the 17αMT induced changes observed in myocardial volume pressure relationships. We report that the steroid-induced changes in the heart are independent of the route of administration of the drug and the elevated blood pressure often associated with anabolic steroid usage (26).

©2000The American College of Sports Medicine

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