There is more to life than revascularization: therapeutic targeting of myocardial ischemia/reperfusion injury.
Ischemic heart disease is the world's leading cause of death, and while clinical advances have meant improved and more rapid revascularization, there remains a significant element of myocardial death that thus far has not been successfully targeted in clinical practice, namely lethal reperfusion injury. Ischemia-reperfusion injury has been the subject of intense research over the last 40 years and our appreciation of the mechanisms of cellular death and salvage have increased immensely over this time, to the extent that a number of clearly identifiable therapeutic targets can now be subjected to clinical trials, as the basic science translates into potentially effective therapies in patients presenting with acute coronary syndromes. In this review, we aim to provide an overview of current evidence regarding the mechanisms of lethal reperfusion injury and endogenous protection, how cardioprotective pharmacological manipulations have been approached to date, and to indicate where therapies may be targeted in the future.
Bell
Robert M
RM
Hatter Institute for Cardiovascular Studies, Chenies Mews, London, UK.
Yellon
Derek M
DM
D000818:Animals; D016923:Cell Death; D006801:Humans; D057775:Ischemic Postconditioning; D019157:Ischemic Preconditioning, Myocardial; D017202:Myocardial Ischemia / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D009204:Myocardial Revascularization / Q000009:adverse effects* / Q000401:mortality; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome