Myocardial infarction: cardioprotection by erythropoietin.
Myocardial infarction: cardioprotection by erythropoietin.
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DOI：
10.1007/978-1-62703-308-4_17
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Latini R
中科院分区：
文献类型：
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作者：
Talan MI;Latini R
近十年来的大量研究表明，单次全身给药促红细胞生成素（EPO）可显著减轻动物（主要是小型啮齿动物）心肌梗死（MI），心肌缺血后再灌注或冠状动脉永久性结扎。这两种方法都进行了批判性的审查，目的是帮助读者了解实验结果转化为临床的关键问题。迄今为止在急性心肌梗死患者中完成的几项临床试验结果未能证明EPO的有益作用，因此对动物模型中获得的结果的有效性提出了质疑。本文对动物实验和临床试验的设计和结果进行了全面的回顾，作者认为在心肌梗死发生期间EPO的治疗窗口非常狭窄，可能在阴性临床试验中被遗漏。心肌梗死大鼠模型实验结果阴性，EPO给药时间与临床试验相似，说明了这一点。未来临床试验的设计应允许EPO的狭窄治疗窗口。考虑到目前从发病到上门和上门到球囊时间的标准，EPO给药的最佳时间应该是在PCI之前。
Extensive research during the last decade demonstrated that a single systemic administration of erythropoietin (EPO) lead to significant attenuation of myocardial infarction (MI) induced in animals, mostly small rodents, either by a myocardial ischemia followed by reperfusion or by a permanent ligation of a coronary artery. Both methods are critically reviewed with the aim of helping the reader in appreciating key issues in the translation of experimental results to the clinic. Results of several clinical trials in patients with acute MI completed to date failed to demonstrate beneficial effects of EPO, and thus put into question the validity of results obtained in animal models. Comprehensive review of design and results of animal experiments and clinical trials presented here allowed authors to postulate that therapeutic window for EPO during developing MI is very narrow and was possibly missed in negative clinical trials. This point was illustrated by the negative outcome of experiment in the rat model of MI in which timing of EPO administration was similar to that in clinical trials. The design of future clinical trials should allow for a narrow therapeutic window of EPO. Given current standards for onset-to-door and door-to-balloon time the optimal time for EPO administration should be just prior to PCI.