Wargovich T J, Mehta J, Nichols W W, Ward M B, Lawson D, Franzini D, Conti C R
Veterans Administration Medical Center, Gainesville, FL.
Am Heart J. 1987 Nov;114(5):1078-85. doi: 10.1016/0002-8703(87)90182-7.
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.
我们研究了一种新型选择性血栓素A2（TXA2）合成酶抑制剂U-63,557A对大鼠左冠状动脉结扎后48小时心肌梗死面积的影响。在冠状动脉结扎前给予单次8mg/kg剂量的U-63,557A（呋格雷酯），血小板聚集和血清TXA2生成在长达48小时内显著下降（p<0.02）。通过对连续左心室切片进行平面测量法测得的心肌梗死面积，从44±3%（生理盐水处理的对照大鼠）降至34±4%（p<0.05）。与生理盐水处理的对照动物相比，U-63,557A处理的动物在冠状动脉结扎后的左心室肌酸激酶（CK）也得到了保留（p<0.05）。U-63,557A的这些有益作用并未伴随着心肌需氧量指标（心率和动脉压）的降低。此外，U-63,557A显著减少了梗死心肌中的中性粒细胞积聚（26±6对96±3/高倍视野 [p<0.01]）。这些数据表明，在冠状动脉结扎前给予单剂量的选择性TXA2合成酶抑制剂可在长达48小时内调节血小板功能，并减少心肌损伤的程度，这可能部分与中性粒细胞积聚的减少有关。
