Talan Mark I, Latini Roberto
Laboratory of Cardiovascular Sciences, National Institute on Aging, NIH, Baltimore, MD, USA.
Methods Mol Biol. 2013;982:265-302. doi: 10.1007/978-1-62703-308-4_17.
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.
过去十年的广泛研究表明，单次全身给予促红细胞生成素（EPO）可显著减轻动物（主要是小型啮齿动物）因心肌缺血再灌注或冠状动脉永久结扎诱导的心肌梗死（MI）。对这两种方法都进行了批判性回顾，目的是帮助读者理解将实验结果转化为临床应用中的关键问题。迄今为止完成的几项针对急性心肌梗死患者的临床试验结果未能证明EPO的有益效果，因此对在动物模型中获得的结果的有效性提出了质疑。此处对动物实验和临床试验的设计及结果进行的全面回顾使作者推测，在心肌梗死发生过程中EPO的治疗窗非常狭窄，在阴性临床试验中可能被错过了。这一点在心肌梗死大鼠模型实验的阴性结果中得到了体现，该实验中EPO给药时间与临床试验相似。未来临床试验的设计应考虑到EPO狭窄的治疗窗。鉴于目前的发病到入院和入院到球囊扩张时间标准，EPO给药的最佳时间应恰好在PCI之前。
