Myocardial protection of contractile function after global ischemia by physiologic estrogen replacement in the ovariectomized rat

The role of physiologic estrogen levels (pg) on postischemic myocardial function was studied in the isolated working rat heart without (n = 28, experiment No. 1) or with (n = 15, experiment No. 2) preconditioning. For experiment No. 1, female ovariectomized rats were treated with placebo (n = 19) or 17 beta-estradiol (E2, n = 9: chronic E2), and 14 days later hearts were removed and perfused with modified Krebs-Henseleit buffer in vitro. In nine placebo-treated rats, E2 was administered at 20 min prior to ischemia (acute E2), The hearts were subjected to 15 min of global ischemia and 20 min of renew, In experiment No. 2, ovariectomized rats were treated with placebo (n = 8) or 17 beta-E2 (chronic E2, n = 7), In this experiment, hearts were first preconditioned and then subjected to 20 min of sustained ischemia followed by 20 min of reflow. Global ischemia was produced by clamping the aorta and restricting left atrial flow so that coronary flow was reduced to zero; hemodynamics were continuously monitored throughout the study, Aortic flow, coronary flow, cardiac output, and dP/dt were assessed at baseline, at the end of the ischemic period, and during reflow. The severity of ischemia was measured by post-ischemic release of lactate, lactate dehydrogenase, and creatine kinase and was similar among all groups in each study. In experiment No. 1, recovery of aortic flow, cardiac output, and dP/dt following reperfusion, was significantly improved in rats treated with chronic E2 (P<0,05); acute E2 had no significant benefit. Post-ischemic recovery of coronary flow was not significantly affected, In experiment No. 2, chronic E2 treatment also significantly improved post-ischemic recovery of cardiac function in preconditioned hearts when compared with controls (P<0,05), In summary, E2 replacement in ovariectomized rats improves contractile function following global ischemia and reflow; cardioprotection by estrogen was observed over and above that conferred by ischemic preconditioning. Since the cardioprotective effect of E2 was independent of a significant improvement in coronary flow a direct effect of the hormone on the cardiac myocytes is postulated. (C) 1997 Academic Press Limited.