Pathophysiology of ischemia-reperfusion injury: experimental data.

Early reperfusion has clearly been shown to be the most effective means to prevent cell death after coronary artery occlusion. It is now widely accepted that the prompt reopening of the occluded vessel, either by mechanical (coronary angioplasty or bypass surgery) or pharmacological means (thrombolytic drugs), should be performed as soon as possible in patients with acute myocardial infarction1-3. However reperfusion of the ischemic myocardium may not always be completely beneficial, and there is now evidence that it may initiate a cascade of events that partially counteract the beneficial effects of blood flow restoration. This phenomenon has been termed “reperfusion injury”1,4. Reperfusion injury may affect various aspects of myocardial and endothelial function, with different and complex pathophysiological consequences5,6. Several key issues in the understanding of reperfusion injury are now clarified. First, ischemic changes are the necessary pre-requisites, but are not in themselves sufficient. Second, analyses after reperfusion do not distinguish cell death caused by ischemia from cell death caused by reperfusion. Third, while reperfusion-induced alterations have been well documented in experimental studies, a clear demonstration of their occurrence in the clinical practice has not been unequivocally obtained (Table I)3. Therefore, the only valid criterion to attribute cell damage to reperfusion injury is by demonstrating that modifications of reperfusion conditions prevent cell death or dysfunction. This paper will review the mechanisms of reperfusion injury and highlight the ample opportunities that such knowledge may open for new therapies of acute myocardial damage initiated by ischemia, highlighting the importance of experimental models to design new intervention strategies. © 2002 CEPI Srl