Protection from Myocardial Reperfusion Injury by Acute Administration of 17β-Estradiol

Although several studies have demonstrated that chronic exposure to estrogen appears to be cardioprotective, acute circulatory effects of estrogen are largely unknown. Therefore, we studied the effects of acute administration of 17β-estradiol in myocardial ischemia/reperfusion. Cats were subjected to 90 min of left anterior descending coronary artery (LAD) occlusion and 270 min of reperfusion (MI/R). Either the estrogenic steroid, 17β-estradiol or its non-estrogenic isomer, 17α-estradiol was administered (i.v.) 30 min prior to reperfusion at 1μg/kg bolus followed by a constant infusion lasting the remaining duration of the protocol at 1μg/kg/h. Control cats were subjected to sham MI/R. Cats treated with 17β-estradiol demonstrated a marked reduction in cardiac necrosis following MI/R compared to cats receiving 17α-estradiol or phosphate buffered saline (17±2%v33±1% or 34±4% area of necrosis indexed to the area-at-risk,P<0.01). In addition, cats receiving 17β-estradiol exhibited reduced myocardial PMN infiltration in necrotic tissue as compared to 17α-estradiol treated cats. Moreover, 17β-estradiol administration attenuated neutrophil adherence toex vivocoronary vascular endothelium compared to the two controls (44±8 PMNs/mm2v79±7 PMNs/mm2or 86±7 PMNs/mm2P<0.01). These data indicate that 17β-estradiol protects against myocardial ischemia/reperfusion, in part, by attenuating PMN infiltration and subsequent injury due to PMN mediator release.