Myocardial triggers involved in remote ischemic preconditioning activation

GARCES M; DONATO M; DEL MAURO JS; MARCHINI T; EVELSON P; HOCHT C; GELPI RJ; GOYENECHE A; PEREZ V; RODRÍGUEZ JM

EXPERIMENTAL PHYSIOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016 vol. 101 p. 708 - 716

0958-0670

It has been proposed that remote ischaemic preconditioning (rIPC) activates a parasympathetic neural pathway. However, the myocardial intracellular mechanism of rIPC remains unclear. Here, we characterized some of the intracellular signals participating as rIPC triggers. Isolated rat hearts were subjected to 30 min of global ischaemia and 120 min of reperfusion (Non-rIPC group). In a second group, before the isolation of the heart, an rIPC protocol (three cycles of hindlimb ischaemia?reperfusion) was performed. The infarct size was measured with tetrazolium staining. Expression/phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) and mitochondrial H2O2 production were evaluated at the end of the rIPC protocol, before myocardial ischaemia?reperfusion. The rIPC significantly decreased the infarct size and induced Akt and eNOS phosphorylation. The protective effect on infarct size was abolished by cervical vagal section, l-NAME (an NO synthesis inhibitor) and 5-hydroxydecanoate (a mitochondrial ATP-dependent K+ channel blocker). Mitochondrial production of H2O2 was increased by rIPC, whereas it was abolished by cervical vagal section, l-NAME and 5-hydroxydecanoate. We conclude that rIPC activates a parasympathetic vagal pathway and a mechanism involving the phosphorylation of Akt and eNOS, the opening of mitocondrial TP-dependent K+ channels and the release of H2O2 by the mitochondria. All these phenomena occur before myocardial ischaemia and could act as triggers of rIPC.