Higo K, Sano J, Karasawa A, Kubo K
Department of Cardiovascular Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Arch Int Pharmacodyn Ther. 1993 May-Jun;323:32-49.
The effect of KW-3635, a novel thromboxane A2 receptor antagonist, on infarct size was examined in anesthetized dogs subjected to 1.5 hr of occlusion of the left anterior descending coronary artery followed by 4.5 hr of reperfusion. KW-3635 (1 mg/kg, i.v.) was administered 1 hr before reperfusion and continuously infused (1 mg/kg/hr, i.v.) throughout the experiment. KW-3635 significantly (p < 0.001) reduced the infarct size (30.5% in the KW-3635-treated group as compared with 58.7% in the vehicle-treated group). KW-3635 almost completely inhibited platelet aggregation (ex vivo) induced by epinephrine (10 microM) + U-46619 (1 microM). KW-3635 attenuated the loss of creatine phosphokinase activity from the ischemic myocardium. Histopathological examination revealed that KW-3635 prevented neutrophil accumulation into the ischemic myocardium, ameliorated eosinophilic changes and inhibited contraction band formation in the ischemic myocardium. These results indicate that KW-3635 has a cardioprotective activity and suggest that the inhibition of activation or accumulation of neutrophils is involved in the cardioprotection following thromboxane A2 receptor blockade.
新型血栓素A2受体拮抗剂KW - 3635对梗死面积的影响在接受左冠状动脉前降支闭塞1.5小时然后再灌注4.5小时的麻醉犬中进行了研究。KW - 3635（1毫克/千克，静脉注射）在再灌注前1小时给药，并在整个实验过程中持续输注（1毫克/千克/小时，静脉注射）。KW - 3635显著（p < 0.001）减小了梗死面积（KW - 3635治疗组为30.5%，而载体治疗组为58.7%）。KW - 3635几乎完全抑制了由肾上腺素（10微摩尔）+ U - 46619（1微摩尔）诱导的血小板聚集（体外）。KW - 3635减轻了缺血心肌中肌酸磷酸激酶活性的丧失。组织病理学检查显示，KW - 3635可防止中性粒细胞积聚到缺血心肌中，改善嗜酸性变化并抑制缺血心肌中收缩带的形成。这些结果表明KW - 3635具有心脏保护活性，并提示对中性粒细胞激活或积聚的抑制参与了血栓素A2受体阻断后的心脏保护作用。
