There is little doubt that the net effect of early reperfusion is beneficial. Experimental studies have clearly shown that there is a wavefront of ischemic cell death, from the endocardium to the epicardium, and that timely reperfusion can halt this "march of necrosis" [1]. On the basis of this and other studies, it has long been assumed that if reperfusion has any detrimental consequences, these consist only in the acceleration of the demise of already irreversibly injured ("condemned") myocytes.
This concept has not gone unchallenged. In 1975 Hearse and co-workers described the paradoxical occurrence of abrupt cell damage in isolated hearts upon reoxygenation after a period of hypoxic perfusion [2]. Those experiments for the first time showed that reintroduction of oxygen may not be entirely beneficial. A number of studies have since shown that, while reperfusion relieves ischemia, it also results in a group of events which might induce a specific myocardial damage, over and above the damage caused by ischemia itself [3]. The mechanisms responsible for the occurrence of this "reperfusion injury" are currently the subject of intensive research. This review will focus on the role played in the pathophysiology of reperfusion injury by toxic oxygen metabolites (oxygen free radicals), which can be generated when oxygen is reintroduced into a previously ischemic tissue [4].
Mechanisms of Free Radical-Mediated Cell Damage
Free radicals are very reactive chemical species, characterized by the presence of an unpaired electron. This characteristic enables radicals to trigger chain reactions, resulting in a peroxidative attack of molecules presenting with unsaturated chemical bonds.