title: The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge.
abstract: The incidence of ST segment elevation myocardial infarction (STEMI) has decreased over the last two decades in developed countries, but mortality from STEMI despite widespread access to reperfusion therapy is still substantial as is the development of heart failure, particularly among an expanding older population. In developing countries, the incidence of STEMI is increasing and interventional reperfusion is often not available. We here review the pathophysiology of acute myocardial infarction and reperfusion, notably the temporal and spatial evolution of ischaemic and reperfusion injury, the different modes of cell death, and the resulting coronary microvascular dysfunction. We then go on to briefly characterize the cardioprotective phenomena of ischaemic preconditioning, ischaemic postconditioning, and remote ischaemic conditioning and their underlying signal transduction pathways. We discuss in detail the attempts to translate conditioning strategies and drug therapy into the clinical setting. Most attempts have failed so far to reduce infarct size and improve clinical outcomes in STEMI patients, and we discuss potential reasons for such failure. Currently, it appears that remote ischaemic conditioning and a few drugs (atrial natriuretic peptide, exenatide, metoprolol, and esmolol) reduce infarct size, but studies with clinical outcome as primary endpoint are still underway.
authors.affiliation: Institute for Pathophysiology, West German Heart and Vascular Center, University of Essen Medical School, Hufelandstr. 55, 45122 Essen, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D057775:Ischemic Postconditioning / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D017566:Microvascular Angina / Q000209:etiology; D015425:Myocardial Reperfusion / Q000009:adverse effects / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D062645:Percutaneous Coronary Intervention / Q000379:methods; D000072657:ST Elevation Myocardial Infarction / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents
keywords: Acute myocardial infarction; Cardioprotection; Coronary microvascular dysfunction; Infarct size; Postconditioning; Preconditioning; Remote conditioning; Reperfusion; Reperfusion injury