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稳定前列环素类似物他前列烯在猫急性心肌缺血再灌注后的内皮及心肌保护作用

Endothelium and myocardial protecting actions of taprostene, a stable prostacyclin analogue, after acute myocardial ischemia and reperfusion in cats.

作者信息

Johnson G, Furlan L E, Aoki N, Lefer A M

机构信息

Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.

出版信息

Circ Res. 1990 May;66(5):1362-70. doi: 10.1161/01.res.66.5.1362.

Abstract

The effects of taprostene, a synthetic prostacyclin analogue, were investigated in a 6-hour model of myocardial ischemia (MI) with reperfusion in anesthetized cats. Taprostene (100 ng/kg/min) was infused intravenously starting 30 minutes postocclusion of the left anterior descending coronary artery followed by reperfusion 1 hour later, and the cats were observed for an additional 4.5 hours. Taprostene infusion resulted in significantly lower plasma creatine phosphokinase activities at every time from 3 to 6 hours for the MI + taprostene group compared with the MI + vehicle group and were not significantly different when compared with sham MI controls. The areas at risk, expressed as a percentage of the total left ventricular weights, were not significantly different between the MI groups. However, the necrotic area expressed as a percentage of the myocardial area at risk was significantly lower in the taprostene-treated cats compared with the untreated MI group (p less than 0.01). Cardiac myeloperoxidase activities indicated that significantly fewer neutrophils were attracted to the area at risk and to the ischemic zone of the MI + taprostene cats when compared with the MI cats given only the vehicle. Data from isolated left anterior descending coronary artery ring preparations removed from hearts after 6 hours of ischemia indicated that the endothelium was damaged by ischemia-reperfusion injury in the untreated cats. However, endothelial dysfunction was not observed in circumflex coronary arteries of ischemic cats or in coronary rings isolated from MI + taprostene cats. Thus, taprostene exerted a significant cardioprotection in cats subjected to ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在麻醉猫的心肌缺血(MI)再灌注6小时模型中,研究了合成前列环素类似物他前列烯的作用。在左冠状动脉前降支闭塞30分钟后开始静脉输注他前列烯(100 ng/kg/分钟),1小时后再灌注,然后对猫额外观察4.5小时。与MI + 赋形剂组相比,MI + 他前列烯组在3至6小时的每个时间点,血浆肌酸磷酸激酶活性均显著降低,与假手术MI对照组相比无显著差异。以左心室总重量的百分比表示的危险区域,在MI组之间无显著差异。然而,与未治疗的MI组相比,他前列烯治疗的猫的坏死面积占危险心肌面积的百分比显著降低(p小于0.01)。心脏髓过氧化物酶活性表明,与仅给予赋形剂的MI猫相比,MI + 他前列烯猫的危险区域和缺血区域吸引的中性粒细胞明显减少。从缺血6小时后的心脏取出的离体左冠状动脉前降支环制备物的数据表明,未治疗的猫的内皮因缺血再灌注损伤而受损。然而,在缺血猫的回旋冠状动脉或从MI + 他前列烯猫分离的冠状动脉环中未观察到内皮功能障碍。因此,他前列烯对遭受缺血和再灌注的猫具有显著的心脏保护作用。(摘要截断于250字)

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