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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.

Medicine & Science in Sports & Exercise: May 2000 - Volume 32 - Issue 5 - p 897-903
Clinical Sciences: Clinically Relevant

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.

Department of Physiology, Louisiana State University Health Sciences Center, School of Medicine, New Orleans, LA 70112

Deceased July 11, 1999.

Submitted for publication September 1998.

Accepted for publication August 1999.

Address for correspondence: Raymond E. Shepherd, Ph.D., FACSM, Department of Physiology, Louisiana State University, Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112-1393; E-mail: rsheph@lsumc.edu.

© 2000 Lippincott Williams & Wilkins, Inc.