ROS IN CARDIAC ISCHEMIC PRE- AND POST-CONDITIONING

Ischemic preconditioning (IP) can be obtained with brief periods (few minutes) of myocardial ischemia before an infarcting/index ischemia. IP limits the severity of the injuries brought about by a subsequent ischemia/reperfusion episode. Also postconditioning (PostC), a series of brief (few seconds) reperfusion/ischemia cycles at reperfusion onset, attenuates ischemia/reperfusion injury. We have shown that PostC protection is not dependent on circulating blood factors or cells. In recent years the main idea was 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 signalling elements of protection in 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 KATP-ROS-dependent mechanism. Intriguingly, and in contrast to the above-described theory of ROS as an obligatory part of reperfusion induced damage, some studies suggest the possibility that some ROS species at low concentrations could protect ischemic hearts against reperfusion injury. Yet, we demonstrated that also ischemic PostC is a cardioprotective phenomenon that requires the intervention of redox signalling to be protective. Moreover, very recently it has been shown that redox signalling is also required at the time of myocardial reperfusion to mediate the cardioprotection elicited by preconditioning. Therefore, our and others results suggest that the role of ROS in reperfusion may be reconsidered as they are not only deleterious.