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

BACKGROUND: The benefits of chronic administration of estrogen to postmenopausal women are well documented; however, the acute effects of exogenous estradiol on myocardium after coronary artery occlusion and reperfusion in male and female animal models are unknown. We tested the influence of acute pretreatment with estradiol on the development of myocardial necrosis in two protocols, studying intact anesthetized female and male rabbits. METHODS AND RESULTS: 17beta-estradiol (1 mg) was given 15 minutes before coronary artery occlusion in the treated groups (n = 10 females, 10 males); control rabbits (n = 11 females, 10 males) received water. All rabbits underwent 30 minutes of coronary artery occlusion and 4 hours of reperfusion. Myocardial blood flow was similar between groups at 10 minutes after treatment and during coronary artery occlusion and reperfusion. Thus estradiol did not increase blood flow. Heart rate and systemic pressure were also similar between groups. Estradiol levels during coronary artery occlusion were 1-8 pg/mL in untreated female and male rabbits and 66 +/- 28 (male) and 352 +/- 273 (female) in treated rabbits. Although the size of the ischemic risk zones was similar in both groups in both protocols, estradiol-treated rabbits of both sexes developed significantly less necrosis. Infarct size as a percent of the risk region was 10 +/- 1% in female estradiol-treated rabbits compared with 23 +/- 5% in controls (P <.03) and 16 +/- 4% in estradiol-treated male rabbits compared with 31 +/- 5% in control males (P =.03). Although male rabbits had larger infarcts than female rabbits, sex was not a significant covariate for infarct size. CONCLUSIONS: Estradiol exerts a protective effect on ischemic myocardium that is not associated with an increase in myocardial blood flow or alteration in hemodynamics. This study shows that acute administration of estrogen before coronary artery occlusion reduces infarct size in both male and female rabbits.