Ischaemic conditioning: pitfalls on the path to clinical translation.
Ischaemic conditioning: pitfalls on the path to clinical translation.
复制标题
缺血调节：临床转化之路上的陷阱。
DOI：
10.1111/bph.13064
复制
发表时间：
2015
影响因子：
7.3
通讯作者：
Przyklenk,Karin
中科院分区：
文献类型：
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作者：
Przyklenk,Karin
能够减轻心肌缺血再灌注损伤和减少梗死面积的新型辅助策略的发展仍然是一个主要的，未满足的临床需求。大量的临床前证据表明，缺血“条件作用”具有深远的心脏保护作用，并将这种现象（特别是后条件作用和远程条件作用的范例）定位为迄今为止确定的最有希望和最有效的临床转化候选者。然而，尽管有这种临床前共识，目前的II期试验一直受到异质性的困扰，最近的荟萃分析结果在很大程度上未能证实显著的益处。因此，临床应用的道路被认为是“令人失望的”和“令人沮丧的”。本综述的目的是讨论可能阻碍缺血性条件作用临床翻译成功的陷阱，重点关注以下问题：(i)适当的临床研究设计和（ii）选择“正确”的临床前模型以促进临床翻译。这篇文章是“调节心灵——通往翻译的途径”主题部分的一部分。要查看本节中的其他文章，请访问http://dx.doi.org/10.1111/bph.2015.172.issue‐8
The development of novel adjuvant strategies capable of attenuating myocardial ischaemia‐reperfusion injury and reducing infarct size remains a major, unmet clinical need. A wealth of preclinical evidence has established that ischaemic ‘conditioning’ is profoundly cardioprotective, and has positioned the phenomenon (in particular, the paradigms of postconditioning and remote conditioning) as the most promising and potent candidate for clinical translation identified to date. However, despite this preclinical consensus, current phase II trials have been plagued by heterogeneity, and the outcomes of recent meta‐analyses have largely failed to confirm significant benefit. As a result, the path to clinical application has been perceived as ‘disappointing’ and ‘frustrating’. The goal of the current review is to discuss the pitfalls that may be stalling the successful clinical translation of ischaemic conditioning, with an emphasis on concerns regarding: (i) appropriate clinical study design and (ii) the choice of the ‘right’ preclinical models to facilitate clinical translation.Linked ArticlesThis article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8