Brezinski M E, Yanagisawa A, Darius H, Lefer A M
Am Heart J. 1985 Dec;110(6):1161-7. doi: 10.1016/0002-8703(85)90006-7.
Thromboxane A2 (TxA2) production increases significantly during acute myocardial ischemia. Since TxA2 induces platelet aggregation, coronary vasoconstriction, and has a direct cytolytic effect, thromboxane receptor antagonism would be expected to be beneficial in acute myocardial ischemia. Thirty minutes after ligation of the left anterior descending coronary artery (LAD) in anesthetized cats, the TxA2 receptor antagonist BM-13,177 or its vehicle was given as a bolus injection at 20 mg/kg, followed by continuous infusion of 20 mg/kg/hr for 4.5 hours. ST segment elevation declined significantly (p less than 0.02) after BM-13,177 treatment, suggesting a reduction in cellular ischemia. The loss in myocardial creatine kinase (CK) activity and in free amino-nitrogen concentration in the ischemic area was also significantly reduced (p less than 0.01). No significant changes in blood pressure or heart rate were seen with BM-13,177 during myocardial ischemia or in nonischemic control cats. Blood levels of BM-13,177 were sufficient to inhibit ex vivo platelet aggregation induced by the prostaglandin endoperoxide analog, U-46,619. Data from isolated cat coronary arteries suggest that BM-13, 177 antagonizes the thromboxane/endoperoxide receptor in coronary vascular smooth muscle. These experiments indicate that TxA2 plays a significant role in propagating the extension of ischemic damage, and that thromboxane receptor antagonism is an effective means of reducing the damage provoked by TxA2 in acute myocardial ischemia.
在急性心肌缺血期间，血栓素A2（TxA2）的生成显著增加。由于TxA2可诱导血小板聚集、冠状动脉血管收缩，并具有直接的细胞溶解作用，因此预计血栓素受体拮抗剂对急性心肌缺血有益。在麻醉猫的左冠状动脉前降支（LAD）结扎30分钟后，以20mg/kg的剂量静脉推注TxA2受体拮抗剂BM-13,177或其溶媒，随后以20mg/kg/小时的速度持续输注4.5小时。BM-13,177治疗后ST段抬高显著下降（p<0.02），提示细胞缺血减轻。缺血区域心肌肌酸激酶（CK）活性和游离氨基氮浓度的损失也显著减少（p<0.01）。在心肌缺血期间或非缺血对照猫中，BM-13,177对血压或心率无显著影响。BM-13,177的血药浓度足以抑制前列腺素内过氧化物类似物U-46,619诱导的体外血小板聚集。来自离体猫冠状动脉的数据表明，BM-13,177可拮抗冠状动脉血管平滑肌中的血栓素/内过氧化物受体。这些实验表明，TxA2在缺血损伤扩展的传播中起重要作用，血栓素受体拮抗是减少TxA2在急性心肌缺血中引起的损伤的有效手段。
