Preconditioning and postconditioning: underlying mechanisms and clinical application.
Coronary heart disease (CHD) is the leading cause of death world-wide. Its major pathophysiological manifestation is acute myocardial ischaemia-reperfusion injury. Innovative treatment strategies for protecting the myocardium against the detrimental effects of this form of injury are required in order to improve clinical outcomes in patients with CHD. In this regard, harnessing the endogenous protection elicited by the heart's ability to 'condition' itself, has recently emerged as a powerful new strategy for limiting myocardial injury, preserving left ventricular systolic function and potentially improving morbidity and mortality in patients with CHD. 'Conditioning' the heart to tolerate the effects of acute ischaemia-reperfusion injury can be initiated through the application of several different mechanical and pharmacological strategies. Inducing brief non-lethal episodes of ischaemia and reperfusion to the heart either prior to, during, or even after an episode of sustained lethal myocardial ischaemia has the capacity to dramatically reduce myocardial injury--a phenomenon termed ischaemic preconditioning (IPC), preconditioning or postconditioning, respectively. Intriguingly, similar levels of cardioprotection can be achieved by applying the brief episodes of non-lethal ischaemia and reperfusion to an organ or tissue remote from the heart, thereby obviating the need to 'condition' the heart directly. This phenomenon has been termed remote ischaemic 'conditioning', and it can offer widespread systemic protection to other organs which are susceptible to acute ischaemia-reperfusion injury such as the brain, liver, intestine or kidney. Furthermore, the identification of the signalling pathways which underlie the effects of 'conditioning', has provided novel targets for pharmacological agents allowing one to recapitulate the benefits of these cardioprotective phenomena--so-termed pharmacological preconditioning and postconditioning. Initial clinical studies, reporting beneficial effects of 'conditioning' the heart to tolerate acute ischaemia-reperfusion injury, have been encouraging. Larger multi-centred randomised studies are now required to determine whether these 'conditioning' strategies are able to impact on clinical outcomes. In this article, we provide an overview of 'conditioning' in all its various forms, describe the underlying mechanisms and review the recent clinical application of this emerging cardioprotective strategy.
Hausenloy
Derek J
DJ
The Hatter Cardiovascular Institute, University College London, United Kingdom.
Yellon
Derek M
DM
D000818:Animals; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D002317:Cardiovascular Agents