Review
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Cardiol. Jun 26, 2011; 3(6): 186-200
Published online Jun 26, 2011. doi: 10.4330/wjc.v3.i6.186
Ischemia/reperfusion injury and cardioprotective mechanisms: Role of mitochondria and reactive oxygen species
Maria-Giulia Perrelli, Pasquale Pagliaro, Claudia Penna
Maria-Giulia Perrelli, Pasquale Pagliaro, Claudia Penna, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
Maria-Giulia Perrelli, Pasquale Pagliaro, Claudia Penna, National Institute of Cardiovascular Research, Bologna, Italy
Author contributions: All authors contributed equally to the review.
Supported by National Institutes of Cardiovascular Research; Regione Piemonte, PRIN, ex-60% and Compagnia di San Paolo, Italy
Correspondence to: Dr. Pasquale Pagliaro, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy. pasquale.pagliaro@unito.it
Telephone: +39-11-6705450 Fax: +39-11-9038639
Received: March 8, 2011
Revised: May 11, 2011
Accepted: May 18, 2011
Published online: June 26, 2011
Abstract

Reperfusion therapy must be applied as soon as possible to attenuate the ischemic insult of acute myocardial infarction (AMI). However reperfusion is responsible for additional myocardial damage, which likely involves opening of the mitochondrial permeability transition pore (mPTP). In reperfusion injury, mitochondrial damage is a determining factor in causing loss of cardiomyocyte function and viability. Major mechanisms of mitochondrial dysfunction include the long lasting opening of mPTPs and the oxidative stress resulting from formation of reactive oxygen species (ROS). Several signaling cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning, obtained with brief intermittent ischemia or with pharmacological agents. These pathways converge on a common target, the mitochondria, to preserve their function after ischemia/reperfusion. The present review discusses the role of mitochondria in cardioprotection, especially the involvement of adenosine triphosphate-dependent potassium channels, ROS signaling, and the mPTP. Ischemic postconditioning has emerged as a new way to target the mitochondria, and to drastically reduce lethal reperfusion injury. Several clinical studies using ischemic postconditioning during angioplasty now support its protective effects, and an interesting alternative is pharmacological postconditioning. In fact ischemic postconditioning and the mPTP desensitizer, cyclosporine A, have been shown to induce comparable protection in AMI patients.

Keywords: Adenosine triphosphate-dependent potassium channels; Cardioprotection; Ischemia-reperfusion injury; Mitochondrial permeability transition pore; Reactive oxygen species