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(Circulation. 2000;102:2983.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Effects of Estrogen Replacement on Infarct Size, Cardiac Remodeling, and the Endothelin System After Myocardial Infarction in Ovariectomized Rats

Paula J. W. Smith, PhD; Olga Ornatsky, PhD; Duncan J. Stewart, MD; Pierre Picard, PhD; Fayez Dawood, DVM; Wen-Hu Wen, MD; Peter P. Liu, MD; David J. Webb, MD; Juan Carlos Monge, MD

From the Terrence Donnelly Heart Centre (P.J.W.S., O.O., D.J.S., P.P., J.C.M.), Division of Cardiology, St. Michael’s Hospital, and the Toronto Hospital (F.D., W.-H.W., P.P.L.), University of Toronto, Toronto, Canada, and the Department of Medicine (P.J.W.S., D.J.W.), University of Edinburgh, Edinburgh, UK.

Correspondence Dr Juan Carlos Monge, Division of Cardiology, St. Michael’s Hospital, 30 Bond St, Toronto, Ontario, Canada M5B 1W8. E-mail mongej{at}smh.toronto.on.ca

Background—Estrogen may increase the long-term survival of women who have suffered from a myocardial infarction (MI). We examined the acute and chronic influence of estrogen on MI in the rat left coronary artery ligation model.

Methods and Results—Female Sprague-Dawley rats (10 to 12 weeks, n=93), divided into 3 groups (rats with intact ovaries, ovariectomized rats administered 17ß-estradiol [17ß-E₂] replacement, and ovariectomized rats administered placebo 2 weeks before MI), were randomized to left coronary artery ligation (n=66) or sham-operated (n=27) groups. Ten to 11 weeks after MI, rats were randomly assigned to either (1) assessment of left ventricular (LV) function and morphometric analysis or (2) measurement of cardiopulmonary mRNA expression of preproendothelin-1 and endothelin A and B receptors. Acutely, estrogen was associated with a trend toward increased mortality. Infarct size was increased in the 17ß-E₂ group compared with the placebo group (42±2% versus 26±3%, respectively; P=0.01). Chronically, wall tension was normalized through a reduction in LV cavity size with estrogen treatment (419±41 mm Hg/mm for 17ß-E₂ versus 946±300 mm Hg/mm for placebo, P=0.039). In the LV, there was a 2.5-fold increase in endothelin B mRNA expression after MI in placebo-treated rats (P=0.004 versus sham-operated rats) that was prevented in the 17ß-E₂ group (P=NS versus sham-operated rats).

Conclusions—These results suggest that estrogen is detrimental at the time of MI or early post-MI period, resulting in an increased size of infarct or infarct expansion, but chronically, it can normalize wall tension and inhibit LV dilatation, which may in turn lead to increased long-term survival. Regulation of the endothelin system, particularly the expression of the endothelin B receptor, may contribute to these estrogenic effects.

Key Words: hormones • myocardial infarction • endothelin

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