Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury--a review.
BACKGROUND
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.


OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Tapuria
Niteen
N
Institute-Hepatobiliary Pancreatic and Liver Transplant Unit, University Department of Surgery, Royal Free and University College School of Medicine, UCL, London, United Kingdom.
Kumar
Yogesh
Y
Habib
Meer Mohammad
MM
Abu Amara
Mahmoud
M
Seifalian
Alexander M
AM
Davidson
Brian R
BR
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology; D005121:Extremities / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D019194:Ischemic Preconditioning / Q000379:methods*; D008833:Microcirculation; D017202:Myocardial Ischemia / Q000503:physiopathology; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013152:Splanchnic Circulation