Myocardial reperfusion injury: looking beyond primary PCI

Eur Heart J. 2013 Jun;34(23):1714-22. doi: 10.1093/eurheartj/eht090. Epub 2013 Mar 27.


Coronary heart disease (CHD) is the leading cause of death and disability in Europe. For patients presenting with an acute ST-segment elevation myocardial infarction (STEMI), timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous coronary intervention (PPCI) is the most effective therapy for limiting myocardial infarct (MI) size, preserving left-ventricular systolic function and reducing the onset of heart failure. Despite this, the morbidity and mortality of STEMI patients remain significant, and novel therapeutic interventions are required to improve clinical outcomes in this patient group. Paradoxically, the process of myocardial reperfusion can itself induce cardiomyocyte death-a phenomenon which has been termed 'myocardial reperfusion injury' (RI), the irreversible consequences of which include microvascular obstruction and myocardial infarction. Unfortunately, there is currently no effective therapy for preventing myocardial RI in STEMI patients making it an important residual target for cardioprotection. Previous attempts to translate cardioprotective therapies (antioxidants, calcium-channel blockers, and anti-inflammatory agents) for reducing RI into the clinic, have been unsuccessful. An improved understanding of the pathophysiological mechanisms underlying RI has resulted in the identification of several promising mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hyperoxaemia), and pharmacological (atrial natriuretic peptide, cyclosporin-A, and exenatide) therapeutic strategies, for preventing myocardial RI, many of which have shown promise in initial proof-of-principle clinical studies. In this article, we review the pathophysiology underlying myocardial RI, and highlight the potential therapeutic interventions which may be used in the future to prevent RI and improve clinical outcomes in patients with CHD.

Keywords: Cardioprotection; Myocardial reperfusion injury; Primary percutaneous coronary intervention; ST-elevation myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / etiology
  • Atrial Natriuretic Factor / therapeutic use
  • Blood Glucose / metabolism
  • Calcium / metabolism
  • Cardiotonic Agents / therapeutic use
  • Cell Death / physiology
  • Coronary Occlusion / etiology
  • Disease Models, Animal
  • Hemorrhage / etiology
  • Humans
  • Hydrogen-Ion Concentration
  • Hyperbaric Oxygenation / methods
  • Hypothermia, Induced / methods
  • Ischemic Postconditioning / methods
  • Microvessels
  • Mitochondria, Heart / physiology
  • Mitochondrial Membrane Transport Proteins / physiology
  • Mitochondrial Permeability Transition Pore
  • Myocardial Contraction / physiology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocarditis / etiology
  • Myocytes, Cardiac / pathology
  • Nitric Oxide / physiology
  • Oxidative Stress / physiology
  • Percutaneous Coronary Intervention*


  • Blood Glucose
  • Cardiotonic Agents
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Nitric Oxide
  • Atrial Natriuretic Factor
  • Calcium