Mecanismos de protección miocárdica a distancia

GOYENECHE M; DONATO MARTIN; PAEZ DIAMELA; GARCÉS MARIANA; MARCHINI TIMOTEO; PEREZ VIRGINIA; GRINSPUN MARTIN; DEL MAURO JULIETA; HOCHT CHRISTIAN; EVELSON PABLO; GELPI RICARDO

Revista argentina de cardiología

Revista argentina de cardiología

Año: 2019

Background: Remote ischemic preconditioning (rIPC) has been suggested to reduce infarct size through the activation ofa parasympathetic 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 byrICP 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 secondgroup, 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 protocola bilateral cervical vagotomy [VS (vagal section)] was performed or atropine (muscarinic receptor blocker), L-NAME (NOsynthesis inhibitor), and 5-HD (mK+ATP channel blocker) was administered, respectively. Infarct size and eNOS phosphorylationwere 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, openingof mitochondrial mK+ATP channels, and the production of mitochondrial H2O2.