Evidence against a role of physiological concentrations of estrogen in post-myocardial infarction remodeling

AbstractOBJECTIVESThe purpose of this study was to examine whether endogenous estrogen deficiency induced by ovariectomy affects chronic left ventricular dysfunction post–myocardial infarction (MI).BACKGROUNDEpidemiologic findings suggest that mortality of postmenopausal women is increased after MI, but the underlying mechanisms are unknown.METHODSRats were either not ovariectomized (non-OVX), ovariectomized (OVX) or ovariectomized and treated with subcutaneous 17-beta-estradiol (E2) pellets (OVX + E2). Two weeks later, animals were sham-operated (Sham) or left coronary artery ligated (MI). Eight weeks later, in vivo echocardiographic and hemodynamic measurements were performed. Thereafter, hearts were isolated and perfused isovolumically.RESULTSMean infarct size was similar among the three MI groups. Ovariectomy decreased serum E2levels (11 ± 4 vs. 49 ± 11 pg/ml in non-OVX, p < 0.01) and increased body weight. These changes were reversed by E2replacement. The degree of cardiac hypertrophy was similar for all groups post-MI. Left ventricular diameters were increased post-MI (8.9 ± 0.4 in non-OVX + MI vs. 6.7 ± 0.2 mm in non-OVX + Sham hearts, p < 0.0001), but OVX or OVX + E2replacement did not alter left ventricular diameters in post-MI and Sham hearts. Left ventricular fractional shortening was severely impaired post-MI (19 ± 2% vs. 50 ± 3 in non-OVX + Sham hearts, p < 0.0001) with no influence of hormonal status. Left ventricular end-diastolic pressure, measured in vivo, was increased in all MI groups without significant differences between groups. Pressure-volume curves, obtained in perfused hearts, demonstrated a right and downward shift with reduced maximum left ventricular developed pressure post-MI (75 ± 6 vs. 108 ± 3 mm Hg in non-OVX + Sham hearts, p < 0.001) and were also unaffected by either OVX or E2replacement.CONCLUSIONSChronic endogenous estrogen deficiency does not have major effects on the development of cardiac hypertrophy, dysfunction and dilation post-MI