Ischaemia, reperfusion and cardioprotection: successes and failures in thejourney from molecule to main

In response to the increasing toll of ischaemic heart disease, the last 50 years have seen an enormous amount of research aimed at understanding the b iology of ischaemia and developing methods to control it. Much of this rese arch has used animal models; in some instances the findings have been trans lated successfully to man, in others they have failed to apply to human isc haemia. Some of the failures may be due to animal models inadequately mimic king the clinical situation-a problem arising from there being is no consen sus on a definition of ischaemia. Despite these difficulties, laboratory re search has led to a detailed molecular and cellular characterization of exp erimental ischaemia. From this has emerged the concept of cardioprotection: identifying key changes in the progression of ischaemic injury and develop ing anti-ischaemic agents to combat these changes, thereby increasing the t olerance of the heart to ischaemia. Effective cardioprotection has been est ablished in the laboratory and has been translated very successfully to man in the arena of cardiac surgery. Unfortunately, because of fundamental con ceptual flaws, the application of anti-ischaemic therapy to management of e volving myocardial infarction has, so far, failed. Laboratory research has revealed the phenomenon of reperfusion injury and, in doing so, established the importance of free radicals and oxidant stress in the genesis of injury during ischaemia and reperfusion. From this, the concept of limiting reperfusion injury has emerged and surgeons have again exploited this concept for the benefit of patients, although cardiologists appear reluctant to combine such an approach with thrombolysis. Recent research has also revealed the remarkable adaptive powers of the hea rt and its ability to increase its tolerance to ischaemia through phenomena such as preconditioning. Although preconditioning undoubtedly occurs in ma n, many hurdles must be overcome before this alternative approach to cardio protection can impact the management of heart disease. (C) 2001 The Europea n Society of Cardiology.