Myocardial protection at a crossroads - The need for translation into clinical therapy
Myocardial protection at a crossroads - The need for translation into clinical therapy
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DOI：
10.1161/01.res.0000137171.97172.d7
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发表时间：
2004-07-23
影响因子：
20.1
通讯作者：
Lathrop, DA
中科院分区：
文献类型：
--
作者：
Bolli, R;Becker, L;Lathrop, DA
在过去的30年里，已经报道了数百种实验干预措施（包括药物和非药物）来保护实验动物的缺血心肌；然而，除了早期再灌注之外，没有一种方法被转化为临床实践。美国国家心肺血液研究所召集了一个工作组，讨论未能转化保护心脏免受缺血和再灌注的潜在疗法的原因，并推荐实现这一目标的新方法。工作组得出的结论是，急性心肌梗死、心脏手术和心脏骤停情况下的心脏保护正处于十字路口。目前确定心脏保护疗法的基础研究方法效率低下且适得其反。三十年来，单中心研究投入了大量资源，但往往得出不确定的结果。需要一种新的范式来消除与基础科学发现转化相关的许多困难。工作组敦促重新关注强调功效和临床相关结果的转化研究，并建议建立一个系统，通过类似临床试验的方法（即使用标准化方法进行盲法、随机、多中心和充分有力的研究）对有前景的心脏保护药物进行严格的临床前测试。国家临床前研究联盟将使重要的基础科学发现合理地转化为临床应用。工作组建议美国国立卫生研究院积极干预，以解决当前阻碍心脏保护疗法转化的问题。他们的具体建议包括建立临床前联盟以及开展两项可能证明有效性的临床研究（腺苷在急性心肌梗塞和心脏手术中的 III 期临床试验）。
Over the past 30 years, hundreds of experimental interventions (both pharmacologic and nonpharmacologic) have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The National Heart, Lung, and Blood Institute convened a working group to discuss the reasons for the failure to translate potential therapies for protecting the heart from ischemia and reperfusion and to recommend new approaches to accomplish this goal. The Working Group concluded that cardioprotection in the setting of acute myocardial infarction, cardiac surgery, and cardiac arrest is at a crossroads. Present basic research approaches to identify cardioprotective therapies are inefficient and counterproductive. For 3 decades, significant resources have been invested in single-center studies that have often yielded inconclusive results. A new paradigm is needed to obviate many of the difficulties associated with translation of basic science findings. The Working Group urged a new focus on translational research that emphasizes efficacy and clinically relevant outcomes, and recommended the establishment of a system for rigorous preclinical testing of promising cardioprotective agents with clinical trial-like approaches (ie, blinded, randomized, multicenter, and adequately powered studies using standardized methods). A national preclinical research consortium would enable rational translation of important basic science findings into clinical use. The Working Group recommended that the National Institutes of Health proactively intervene to remedy current problems that impede translation of cardioprotective therapies. Their specific recommendations include the establishment of a preclinical consortium and the performance of 2 clinical studies that are likely to demonstrate effectiveness (phase III clinical trials of adenosine in acute myocardial infarction and cardiac surgery).