The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge

Eur Heart J. 2017 Mar 14;38(11):774-784. doi: 10.1093/eurheartj/ehw224.


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.

Keywords: Acute myocardial infarction; Cardioprotection; Coronary microvascular dysfunction; Infarct size; Postconditioning; Preconditioning; Remote conditioning; Reperfusion; Reperfusion injury.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiotonic Agents / therapeutic use
  • Coronary Circulation / physiology
  • Disease Models, Animal
  • Humans
  • Ischemic Postconditioning / methods
  • Ischemic Preconditioning, Myocardial / methods
  • Microvascular Angina / etiology
  • Myocardial Reperfusion / adverse effects
  • Myocardial Reperfusion / methods*
  • Myocardial Reperfusion Injury / prevention & control
  • Percutaneous Coronary Intervention / methods
  • ST Elevation Myocardial Infarction / etiology*
  • ST Elevation Myocardial Infarction / physiopathology
  • ST Elevation Myocardial Infarction / therapy
  • Single Photon Emission Computed Tomography Computed Tomography / methods
  • Treatment Outcome


  • Cardiotonic Agents