Hock C E, Phillips G R, Lefer A M
Prostaglandins Leukot Med. 1985 Mar;17(3):339-46. doi: 10.1016/0262-1746(85)90124-6.
U-63,557A, a new selective thromboxane synthetase inhibitor, was evaluated for its ability to prevent the extension of myocardial infarct size. Left coronary arteries of male Sprague-Dawley rats (230 - 270 g) were acutely ligated, producing a consistent model of myocardial infarction (MI) in rats analyzed 48 hours later. Left ventricular free wall (LVFW), creatine kinase (CK) activity, and amino-nitrogen concentrations were assayed as indices of infarct size. U-63,557A was administered intravenously in two doses (4 and 8 mg/kg) with a split schedule (2 min post-ischemia and either 4 or 24 hrs later). Administration of the thromboxane synthetase inhibitor significantly reduced both myocardial CK and amino-nitrogen loss at a dose of 8 mg/kg, but it was only slightly effective at 4 mg/kg. Drug treatment significantly increased the percent LVFW spared; 27 +/- 3% (vehicle) vs 43 +/- 7% and 52 +/- 7% (8 mg/kg). U-63,557A is an effective agent in myocardial ischemia for limiting the extension of infarct size after acute coronary artery ligation. Previous studies of other thromboxane synthetase inhibitors showed effectiveness in the early stages of MI. This study shows an effect on true infarct size 48 hours post-ligation, and suggests that inhibition of thromboxane A2 plays an important role in the pathogenesis of ischemic damage in the myocardium.
新型选择性血栓素合成酶抑制剂U - 63,557A被评估了预防心肌梗死面积扩大的能力。对雄性Sprague - Dawley大鼠（230 - 270克）的左冠状动脉进行急性结扎，在48小时后分析时建立了大鼠一致的心肌梗死（MI）模型。测定左心室游离壁（LVFW）、肌酸激酶（CK）活性和氨基氮浓度作为梗死面积的指标。U - 63,557A以两种剂量（4和8毫克/千克）静脉给药，采用分次给药方案（缺血后2分钟以及4或24小时后）。血栓素合成酶抑制剂在8毫克/千克剂量时显著降低了心肌CK和氨基氮的损失，但在4毫克/千克时效果甚微。药物治疗显著增加了未梗死的LVFW百分比；分别为27±3%（赋形剂组）、43±7%和52±7%（8毫克/千克组）。U - 63,557A是一种在心肌缺血中有效的药物，可限制急性冠状动脉结扎后梗死面积的扩大。此前对其他血栓素合成酶抑制剂的研究表明在心肌梗死早期有效。本研究显示在结扎后48小时对实际梗死面积有影响，并表明抑制血栓素A2在心肌缺血性损伤的发病机制中起重要作用。
