PROTECTION FROM MYOCARDIAL REPERFUSION INJURY BY ACUTE ADMINISTRATIONOF 17-BETA-ESTRADIOL

Although several studies have demonstrated that chronic exposure to es trogen appears to be cardioprotective. a acute circulatory effects of estrogen are largely unknown, Therefore, we studied the effects of acu te administration of 17 beta-estradiol in myocardial ischemia/reperfus ion. Cats were subjected to 90 min of left anterior descending coronar y artery (LAD) occlusion and 270 min of reperfusion (MI/R). Either the estrogenic steroid, 17 beta-estradiol or its non-estrogenic isomer, 1 7 alpha-estradiol was administered (i.v.) 30 min prior to reperfusion at 1 mu g/kg bolus followed by a constant infusion lasting the remaini ng duration of the protocol at 1 mu g/kg/h. Control cats were subjecte d to sham MI/R. Cats treated with 17 beta-estradiol demonstrated a mar ked reduction in cardiac necrosis following MI/R compared to cats rece iving 17 alpha-estradiol or phosphate buffered saline (17 +/- 2% v 33 +/- 1% or 34 +/- 4% area of necrosis indexed to the area-at-risk, P<0. 01). In addition, cats receiving 17 beta-estradiol exhibited reduced m yocardial PMN infiltration in necrotic tissue as compared to 17 alpha- estradiol treated cats, Moreover, 17 beta-estradiol administration att enuated neutrophil adherence to ex vivo coronary vascular endothelium compared to the two controls (44 +/- 8 PMNs/mm(2) v 79 +/- 7 PMNs/mm(2 ) or 86 +/- 7 PMNs/mm(2) P<0.01). These data indicate that 17 beta-est radiol protects against myocardial ischemia/reperfusion, in part, by a ttenuating PMN infiltration and subsequent injury due to PMN mediator release.