New Pharmacological Approaches to the Prevention of Myocardial Ischemia- Reperfusion Injury

Curr Drug Targets. 2017;18(15):1689-1711. doi: 10.2174/1389450116666151001112020.

Abstract

Background: Early reperfusion of the blocked vessel is critical to restore the blood flow to the ischemic myocardium to salvage myocardial tissue and improve clinical outcome. This reperfusion strategy after a period of ischemia, however, may elicit further myocardial damage named myocardial reperfusion injury. The manifestations of reperfusion injury include arrhythmias, myocardial stunning and micro-vascular dysfunction, in addition to significant cardiomyocyte death. It is suggested that an overproduction of reactive oxygen species, intracellular calcium overload and inflammatory cell infiltration are the most important features of myocardial ischemia-reperfusion injury.

Objective: In this review, various pharmacological interventions to treat myocardial reperfusion injury including the antioxidant flavonols, hydrogen sulfide, adenosine, opioids, incretin-based therapies and cyclosporin A which targets the mitochondrial permeability transition pore are discussed.

Conclusion: The processes involved in reperfusion injury might provide targets for improved outcomes after myocardial infarction but thus far that aim has not been met in the clinic.

Keywords: Cardioprotection; adenosine; antioxidant; cyclosporin A; flavonol; hydrogen sulfide; incretin-based therapies; ischemia-reperfusion; opioids; reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Calcium / metabolism
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use
  • Humans
  • Mitochondrial Membrane Transport Proteins / drug effects
  • Mitochondrial Permeability Transition Pore
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / prevention & control*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / prevention & control*
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Cardiotonic Agents
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Reactive Oxygen Species
  • Cyclosporine
  • Calcium