Comparison of cardioprotective efficacy of two thromboxane A2 receptor antagonists.
Comparison of cardioprotective efficacy of two thromboxane A2 receptor antagonists.
复制标题
两种血栓素 A2 受体拮抗剂的心脏保护功效比较。
DOI：
10.1097/00005344-200303000-00018
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发表时间：
2003
影响因子：
3
通讯作者：
Gross,GarrettJ
中科院分区：
文献类型：
--
作者：
Ge,Zhi-Dong;Auchampach,JohnA;Piper,GalenM;Gross,GarrettJ
本研究的目的是比较两种结构无关的血栓素a2 （txa2）受体拮抗剂KT2-962和daltroban （bm13.505）在狗心肌缺血/再灌注损伤模型中的疗效。戊巴比妥麻醉犬左旋冠状动脉闭塞90分钟，再灌注5小时。冠状动脉闭塞前10分钟静脉给药，KT2-962 （10 mg/kg）或daltroban （10 mg/kg）。在整个实验过程中测量全身血流动力学，并用放射性微球技术测量局部心肌血流。再灌注期结束时，用氯化三苯四唑染色定量心肌梗死面积。KT2-962和daltroban均未显著改变心率、平均动脉血压或局部心肌血流量。缺血/再灌注组织中髓过氧化物酶活性（中性粒细胞浸润指标）的含量在三个治疗组之间无显著差异。然而，给药KT2-962，而不是daltroban，显着降低了缺血期间心室颤动的发生率，并显着降低了心肌梗死面积占危险区域的百分比（约40%）。随后使用电子自旋共振波谱法进行的体外分析表明，KT2-962抑制羟基自由基的形成，而daltroban则没有影响。这些结果表明，KT2-962的有益作用可能是由于其直接清除自由基的特性，而不是其阻断txa2受体的能力。
The purpose of the current study was to compare the efficacy of two structurally unrelated thromboxane A 2 (TXA 2) receptor antagonists, KT2–962 and daltroban (BM 13.505), in a dog model of myocardial ischemia/reperfusion injury. Pentobarbital-anesthetized dogs were subjected to left circumflex coronary artery occlusion for 90 minutes followed by 5 hours of reperfusion. Vehicle, KT2–962 (10 mg/kg), or daltroban (10 mg/kg) were administered as intravenous boluses 10 minutes before coronary occlusion. Systemic hemodynamics were measured throughout the experiments and regional myocardial blood flow was measured by the radioactive microsphere technique. At the end of the reperfusion period, myocardial infarct size was quantified by staining with triphenyltetrazolium chloride. Neither KT2–962 nor daltroban significantly altered heart rate, mean arterial blood pressure, or regional myocardial blood flow. The content of myeloperoxidase activity in the ischemic/reperfused tissue, an index of neutrophil infiltration, was not significantly different among the three treatment groups. However, administration of KT2–962, but not daltroban, significantly reduced the incidence of ventricular fibrillation during the ischemic period and significantly reduced myocardial infarct size expressed as a percentage of the risk region (approximately 40%). Subsequent in-vitro assays using electron spin resonance spectroscopy demonstrated that KT2–962 inhibited the formation of hydroxyl radicals, whereas daltroban had no effect. These results suggest that the beneficial effects of KT2–962 may be due to its direct free radical scavenging properties rather than its ability to block TXA 2 receptors.