The role of aldosterone inhibitors in cardiac ischemia-reperfusion injury

Can J Physiol Pharmacol. 2021 Jan;99(1):18-29. doi: 10.1139/cjpp-2020-0276. Epub 2020 Aug 15.

Abstract

Myocardial ischaemia-reperfusion (I/R) injury is a well-known term for exacerbation of cellular destruction and dysfunction after the restoration of blood flow to a previously ischaemic heart. A vast number of studies that have demonstrated that the role of mineralocorticoids in cardiovascular diseases is based on the use of pharmacological mineralocorticoid receptor (MR) antagonists. This review paper aimed to summarize current knowledge on the effects of MR antagonists on myocardial I/R injury as well as postinfarction remodeling. Animal models, predominantly the Langendorff technique and left anterior descending coronary artery occlusion, have confirmed the potency of MR antagonists as preconditioning and postconditioning agents in limiting infarct size and postinfarction remodeling. Several preclinical studies in rodents have established and proved possible mechanisms of cardioprotection by MR antagonists, such as reduction of oxidative stress, reduction of inflammation, and apoptosis, therefore limiting the infarct zone. However, the results of some clinical trials are inconsistent, since they reported no benefit of MR antagonists in acute myocardial infarction. Due to this, further studies and the results of ongoing clinical trials regarding MR antagonist administration in patients with acute myocardial infarction are being awaited with great interest.

Keywords: aldosterone inhibitors; animal models; clinical models; inhibiteurs de l’aldostérone; ischemia–reperfusion; ischémie–reperfusion; modèles chez les animaux; modèles cliniques.

Publication types

  • Review

MeSH terms

  • Aldosterone / metabolism*
  • Animals
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Heart Ventricles / drug effects
  • Heart Ventricles / physiopathology
  • Humans
  • Incidence
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control
  • Myocardial Reperfusion Injury / epidemiology*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control
  • Myocardium / metabolism
  • Myocardium / pathology
  • Treatment Outcome
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / physiology
  • Ventricular Remodeling / drug effects
  • Ventricular Remodeling / physiology

Substances

  • Cardiotonic Agents
  • Mineralocorticoid Receptor Antagonists
  • Aldosterone