Myocardial triggers involved in activation of remote ischaemic preconditioning

DONATO MARTIN; GOYENECHE M; GARCÉS MARIANA; MARCHINI TIMOTEO; PEREZ VIRGINIA; DEL MAURO JULIETA; HOCHT CHRISTIAN; RODRIGUEZ MANUEL; EVELSON PABLO; RICARDO JORGE GELPI

QUARTERLY JOURNAL OF EXPERIMENTAL PHYSIOLOGY AND COGNATE MEDICAL SCIENCES

CAMBRIDGE UNIV PRESS

Año: 2016

0033-5541

It has been proposed that remote ischaemic preconditioning (rIPC) activates a parasympatheticneural pathway. However, the myocardial intracellular mechanism of rIPC remains unclear.Here, we characterized some of the intracellular signals participating as rIPC triggers. Isolatedrat hearts were subjected to 30 min of global ischaemia and 120 min of reperfusion (Non-rIPCgroup). In a second group, before the isolation of the heart, an rIPC protocol (three cyclesof hindlimb ischaemia?reperfusion) was performed. The infarct size was measured withtetrazolium 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 andinduced Akt and eNOS phosphorylation. The protective effect on infarct size was abolishedby cervical vagal section, l-NAME (an NO synthesis inhibitor) and 5-hydroxydecanoate(a mitochondrial ATP-dependent K+ channel blocker). Mitochondrial production of H2O2was increased by rIPC, whereas it was abolished by cervical vagal section, l-NAME and5-hydroxydecanoate. We conclude that rIPC activates a parasympathetic vagal pathway anda mechanism involving the phosphorylation of Akt and eNOS, the opening of mitochondrial ATP-dependent K+ channels and the release ofH2O2 by themitochondria. All these phenomenaoccur before myocardial ischaemia and could act as triggers of rIPC.