Remote Mechanisms of Myocardial Protection

Abstract

Background: Remote ischemic preconditioning (rIPC) has been suggested to reduce infarct size through the activation of a parasym- pathetic neural pathway. However, the intracellular mechanisms responsible for this protection remain unclear. Objective: The aim of this study was to describe some of the intracellular protective signals activated at the cardiac level by rIPC prior to myocardial ischemia. Methods: Isolated rat hearts were subjected to 30 minutes of global ischemia and 120 minutes of reperfusion (I/R). In a second group, before the isolation of the heart, a rIPC protocol (three cycles of left femoral artery ischemia/reperfusion) was performed, followed by the I/R protocol. Additionally, four experimental groups were studied, in which prior to the rIPC protocol a bilateral cervical vagotomy (VS (vagal section)) was performed or atropine (muscarinic receptor blocker), L-NAME (NO synthesis inhibitor), and 5-HD (mK + ATP channel blocker) was administered, respectively. Infarct size and eNOS phosphorylation were measured in I/R, rIPC, and VS groups. Finally, mitochondrial H2O2 production was assessed. Results: Remote ischemic preconditioning significantly decreased infarct size and this effect was abolished by VS and atropine, L-NAME, and 5-HD treatments. Furthermore, rIPC increased eNOS phosphorylation and this effect was abolished by VS. Finally, rIPC increased the mitochondrial H2O2 production, and this effect was also abolished by VS. Conclusions: Remote ischemic preconditioning activates a muscarinic vagal pathway involving eNOS phosphorylation, opening of mitochondrial mK + ATP channels, and the production of mitochondrial H2O2.