Cardioprotection: a radical view Free radicals in pre and postconditioning.

Abstract

A series of brief (a few minutes) ischemia/reperfusion cycles (ischemic preconditioning, IP) limits myocardial injury produced by a subsequent prolonged period of coronary artery occlusion and reperfusion. Postconditioning (PostC), which is a series of brief (a few seconds) reperfusion/ischemia cycles at reperfusion onset, attenuates also ischemia/reperfusion injury. In recent years the main idea has been that reactive oxygen species (ROS) play an essential, though double-edged, role in cardioprotection: they may participate in reperfusion injury or may play a role as signaling elements of protection in the pre-ischemic phase. It has been demonstrated that preconditioning triggering is redox-sensitive, using either ROS scavengers or ROS generators. We have shown that nitroxyl triggers preconditioning via pro-oxidative, and/or nitrosative stress-related mechanism(s). Several metabolites, including acetylcholine, bradykinin, opioids and phenylephrine, trigger preconditioning-like protection via a mitochondrial K(ATP)-ROS-dependent mechanism. Intriguingly, and contradictory to the above mentioned theory of ROS as an obligatory part of reperfusion-induced damage, some studies suggest the possibility that some ROS at low concentrations could protect ischemic hearts against reperfusion injury. Yet, we demonstrated that ischemic PostC is also a cardioprotective phenomenon that requires the intervention of redox signaling to be protective. Emerging evidence suggests that in a preconditioning scenario a redox signal is required during the first few minutes of myocardial reperfusion following the index ischemic period. Intriguingly, the ROS signaling in the early reperfusion appear crucial to both preconditioning- and postconditioning-induced protection. Therefore, our and others' results suggest that the role of ROS in reperfusion may be reconsidered as they are not only deleterious.

• Authors: Claudia Penna, Daniele Mancardi, Raffaella Rastaldo, Pasquale Pagliaro
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1787 Issue 7 Pg. 781-93 (Jul 2009) ISSN: 0006-3002 [Print] Netherlands
• PMID: 19248760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Free Radicals
• Reactive Oxygen Species

Topics

• Animals
• Free Radicals (metabolism)
• Humans
• Ischemic Preconditioning, Myocardial
• Models, Biological
• Myocardial Reperfusion
• Myocardial Reperfusion Injury (metabolism, physiopathology, prevention & control)
• Myocardium (metabolism, pathology)
• Oxidation-Reduction
• Reactive Oxygen Species (metabolism)
• Signal Transduction