Reduction in myocardial neutrophil accumulation and infarct size following administration of thromboxane inhibitor U-63,557A

Abstract

We examined the effects of a new selective thromboxane A2 (TXA2) synthetase inhibitor, U-63,557A, on myocardial infarct size 48 hours following left coronary ligation in rats. With a single 8 mg/kg dose of U-63,557A (furegrelate) administered prior to coronary ligation, platelet aggregation and serum TXA2 formation declined significantly (p less than 0.02) for up to 48 hours. Myocardial infarct size, as measured by planimetry of serial left ventricular sections, was decreased from 44 +/- 3% (saline-treated control rats) to 34 +/- 4% (p less than 0.05). Left ventricular creatine kinase (CK) following coronary ligation was also preserved in U-63,557A vs saline-treated control animals (p less than 0.05). These beneficial effects of U-63,557A were not accompanied by reduction in the indices of myocardial oxygen demand (heart rate and arterial pressure). Furthermore, neutrophil accumulation in the infarcted myocardium was significantly decreased by U-63,557A (26 +/- 6 vs 96 +/- 3/high-power field [p less than 0.01]). These data suggest that administration of a single dose of selective TXA2 synthetase inhibitor prior to coronary ligation modulates platelet function for up to 48 hours and reduces the extent of myocardial injury, which may, in part, relate to decrease in neutrophil accumulation.