Tapuria Niteen, Kumar Yogesh, Habib Meer Mohammad, Abu Amara Mahmoud, Seifalian Alexander M, Davidson Brian R
Institute-Hepatobiliary Pancreatic and Liver Transplant Unit, University Department of Surgery, Royal Free and University College School of Medicine, UCL, London, United Kingdom.
J Surg Res. 2008 Dec;150(2):304-30. doi: 10.1016/j.jss.2007.12.747. Epub 2008 Jan 22.
Restoration of blood supply to an organ after a critical period of ischemia results in parenchymal injury and dysfunction of the organ referred to as reperfusion injury. Ischemia reperfusion injury is often seen in organ transplants, major organ resections and in shock. Ischemic preconditioning (IPC) is an adaptational response of briefly ischemic tissues which serves to protect against subsequent prolonged ischemic insults and reperfusion injury. Ischemic preconditioning can be mechanical or pharmacological. Direct mechanical preconditioning in which the target organ is exposed to brief ischemia prior to prolonged ischemia has the benefit of reducing ischemia-reperfusion injury (IRI) but its main disadvantage is trauma to major vessels and stress to the target organ. Remote (inter organ) preconditioning is a recent observation in which brief ischemia of one organ has been shown to confer protection on distant organs without direct stress to the organ.
To discuss the evidence for remote IPC (RIPC), underlying mechanisms and possible clinical applications of RIPC. METHODS OF SEARCH: A Pubmed search with the keywords "ischemic preconditioning," "remote preconditioning," "remote ischemic preconditioning," and "ischemia reperfusion" was done. All articles on remote preconditioning up to September 2006 have been reviewed. Relevant reference articles from within these have been selected for further discussion.
Experimental studies have demonstrated that the heart, liver, lung, intestine, brain, kidney and limbs are capable of producing remote preconditioning when subjected to brief IR. Remote intra-organ preconditioning was first described in the heart where brief ischemia in one territory led to protection in other areas. Translation of RIPC to clinical application has been demonstrated by the use of brief forearm ischemia in preconditioning the heart prior to coronary bypass and in reducing endothelial dysfunction of the contra lateral limb. Recently protection of the heart has been demonstrated by remote hind limb preconditioning in children who underwent surgery on cardiopulmonary bypass for congenital heart disease. The RIPC stimulus presumably induces release of biochemical messengers which act either by the bloodstream or by the neurogenic pathway resulting in reduced oxidative stress and preservation of mitochondrial function. Studies have demonstrated endothelial NO, Free radicals, Kinases, Opioids, Catecholamines and K(ATP) channels as the candidate mechanism in remote preconditioning. Experiments have shown suppression of proinflammatory genes, expression of antioxidant genes and modulation of gene expression by RIPC as a novel method of IRI injury prevention.
There is strong evidence to support RIPC. The underlying mechanisms and pathways need further clarification. The effective use of RIPC needs to be investigated in clinical settings.
在一段关键的缺血期后恢复器官的血液供应会导致实质损伤以及器官功能障碍，即所谓的再灌注损伤。再灌注损伤常见于器官移植、大型器官切除以及休克情况中。缺血预处理（IPC）是短暂缺血组织的一种适应性反应，可保护组织免受随后长时间的缺血损伤和再灌注损伤。缺血预处理可分为机械性和药物性。直接机械预处理是指在长时间缺血之前使靶器官短暂缺血，其优点是能减少缺血 - 再灌注损伤（IRI），但主要缺点是对大血管造成创伤以及给靶器官带来压力。远程（器官间）预处理是最近的一项观察发现，即一个器官的短暂缺血已被证明能对远处器官提供保护，而不会对该器官造成直接压力。
探讨远程缺血预处理（RIPC）的证据、潜在机制及其可能的临床应用。
在PubMed上以“缺血预处理”、“远程预处理”、“远程缺血预处理”和“缺血再灌注”为关键词进行检索。对截至2006年9月的所有关于远程预处理的文章进行了综述。从这些文章中挑选了相关参考文献进行进一步讨论。
实验研究表明，心脏、肝脏、肺、肠道、大脑、肾脏和四肢在经历短暂的缺血再灌注时能够产生远程预处理。远程器官内预处理最早在心脏中被描述，即一个区域的短暂缺血会导致其他区域得到保护。通过在冠状动脉搭桥术前对心脏进行短暂的前臂缺血预处理以及减少对侧肢体的内皮功能障碍，已证明RIPC可转化为临床应用。最近，在接受先天性心脏病体外循环手术的儿童中，通过远程后肢预处理证明了对心脏的保护作用。RIPC刺激可能会诱导生化信使的释放，这些信使通过血液循环或神经源性途径发挥作用，从而减少氧化应激并保护线粒体功能。研究表明内皮一氧化氮、自由基、激酶、阿片类物质、儿茶酚胺和K（ATP）通道是远程预处理的候选机制。实验表明，抑制促炎基因、抗氧化基因的表达以及RIPC对基因表达的调节是预防IRI损伤的一种新方法。
有强有力的证据支持RIPC。其潜在机制和途径需要进一步阐明。需要在临床环境中研究RIPC的有效应用。
