746-4 Estradiol, Administered Acutely, Protects Ischemic Myocardium in Both Female and Male Rabbits

Abstract

Premenopausal women are at lower risk of coronary heart disease than their male counterparts, and it has been shown that estrogen treatment protects against cardiovascular disease in postmenopausal women. The acute cardiac effects are unknown. We investigated the effect of acute pretreatment with estradiol on myocardial infarct size in 2 protocols, studying intact anesthetized female and male rabbits. 17β-estradiol (1 mg) was given 15 min before coronary artery occlusion in the treated group; control rabbits received vehicle. All rabbits underwent 30 min of coronary artery occlusion and 4 hrs reperfusion. Risk zone (RZ) was assessed by blue dye and infarct size (IS) by tetrazolium staining. Differences in postischemic function were assessed by dP/dt at 4 hr of reperfusion. Myocardial blood flow was similar between groups 10 min after treatment and during occlusion and reperfusion, thus estradiol did not increase blood flow. Heart rate and systemic pressure were also similar between groups. Estradiol levels during occlusion were 1-8 picogramfml in untreated female and male rabbits and 66 ± 28 (male) and 352 ± 273 (female) in treated rabbits. Treated rabbits of both sexes developed significantly less necrosis. Although male rabbits had larger infarcts than female rabbits, gender was not a significant covariate for IS. Functional recovery at 4 hr reperfusion was not improved by estradiol in either protocol.GroupEmpty CellnRZ(%LV)IS(% RZ)dP/dt†FemaleControl1129 ± 223 ± 560 ± 6Estradiol1029 ± 310 ± l*77 ± 4MaleControl1035 ± 231 ± 569 ± 7Estradiol1034 ± 316 ± 4*68 ± 6*p < 0.03 vs respective control group†(% baseline) p = ns between groups by ANOVA p < 0.03 vs respective control group (% baseline) p = ns between groups by ANOVA Estradiol exerts a protective effect on ischemic myocardium that is not associated with an increase in myocardial blood flow or alteration in hemodynamics. This is the first study, of which we are aware, showing that acute administration of estrogen reduces infarct size.