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急性心肌梗死中心肌保护药物的临床转化现状。

Current state of clinical translation of cardioprotective agents for acute myocardial infarction.

机构信息

Division of Cardiovascular Medicine, Department of Medicine, Heart Institute, Good Samaritan Hospital, Los Angeles, CA 90017, USA.

出版信息

Circ Res. 2013 Aug 2;113(4):451-63. doi: 10.1161/CIRCRESAHA.112.300627.

Abstract

There is continued interest in the concept of limiting myocardial infarct size with adjunctive agents administered along with reperfusion injury; however, there remains considerable controversy in the literature. The purpose of this article is to review the medical literature on clinical trials performed during the past 3 years that have attempted to reduce myocardial infarct size by administration of adjunctive therapies along with reperfusion therapy. A PubMed-driven literature search revealed a host of clinical trials focusing on the following prominent types of therapies: endogenous conditioning (postconditioning and remote ischemic conditioning); rapid cooling; pharmacological therapy (cyclosporine, abciximab, clopidogrel, tirofiban, erythropoietin, thrombus aspiration, adenosine, glucose-insulin-potassium, statins, antidiabetic agents, FX06, iron chelation, and ranolazine). Although there remains some controversy, quite a few of these studies showed that adjunctive therapy further reduced myocardial infarct size when coupled with reperfusion. Antiplatelet agents are emerging as some of the newest agents that seem to have cardioprotective capabilities. Postconditioning has become a bit more controversial in the clinical literature; remote conditioning, early and rapid cooling, adenosine, and ranolazine are intriguing therapies deserving of larger studies. Certain agents and maneuvers, such as erythropoietin, protein kinase C δ inhibitors, iron chelation, and intra-aortic balloon counterpulsation, perhaps should be retired. The correct adjunctive therapy administered along with reperfusion has the capability of further reducing myocardial injury during ST-segment-elevation myocardial infarction.

摘要

人们一直对通过在再灌注损伤时联合辅助药物来限制心肌梗死面积的概念感兴趣;然而,文献中仍存在相当大的争议。本文的目的是回顾过去 3 年中进行的临床试验的医学文献,这些试验试图通过在再灌注治疗的同时给予辅助治疗来减少心肌梗死面积。通过 PubMed 驱动的文献检索,发现了许多临床试验,主要集中在以下几种突出的治疗类型上:内源性预处理(后处理和远程缺血预处理);快速冷却;药物治疗(环孢素、阿昔单抗、氯吡格雷、替罗非班、促红细胞生成素、血栓抽吸、腺苷、葡萄糖-胰岛素-钾、他汀类药物、降糖药物、FX06、铁螯合、雷诺嗪)。尽管仍存在一些争议,但相当多的这些研究表明,当与再灌注联合使用时,辅助治疗进一步减少了心肌梗死面积。抗血小板药物作为一些具有心脏保护能力的最新药物正在出现。后处理在临床文献中变得更加有争议;远程预处理、早期和快速冷却、腺苷和雷诺嗪是一些值得进一步研究的有趣的治疗方法。某些药物和操作,如促红细胞生成素、蛋白激酶 C δ 抑制剂、铁螯合和主动脉内球囊反搏,可能应该被淘汰。在 ST 段抬高型心肌梗死期间,与再灌注联合使用的正确辅助治疗有能力进一步减少心肌损伤。

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