Mechanisms, management and future directions for reperfusion injury after acute myocardial infarction.
Animal models of sustained ischemia have shown exacerbation of myocardial injury during reperfusion, mediated largely by cytotoxic effects of free radical generation, complement activation, shifts in substrate use and inflammation. On the basis of current understanding of the pathogenesis of reperfusion injury, numerous therapies have shown a reduction in infarct size and improved ventricular function in animal models. Clinical trial experience has, however, so far been disappointing for the use of these therapies in patients with acute myocardial infarction (MI), being associated with no or inconsistent benefit to left-ventricular function, complications of MI or survival. The growing emphasis on early revascularization with primary coronary intervention and stenting in the management acute MI, with the potential for more complete drug delivery to injured myocardium, could provide greater opportunities for pharmacologic cardioprotection as adjunctive therapy in the future.
Cannon
Richard O
RO
Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. cannonr@nih.gov
D000818:Animals; D017209:Apoptosis; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications* / Q000601:surgery; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D009204:Myocardial Revascularization; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides