Myocardial protection induced by vagal stimulation

EDUARDO A. BERNATENÉ; JAZMÍN KELLY; NAHUEL MÉNDEZ DIODATI; RICARDO J. GELPI; BRUNO BUCHHOLZ

CABA

Simposio; VI Postdoctoral Joint Meeting on Cardiovascular Sciences; 2018

Instituto de Fisiopatología Cardiovascular, Facultad de Medicina, Universidad de Buenos Aires; International Academy of Cardiovascular Science; ServCor Sao Francisco de Assis Cardiovascular Founda.

Vagal stimulation (VS) during myocardial ischemia and reperfusion has beneficialeffects. However, it is not known whether short-term VS applied prior to ischemia or at the onset of reperfusion protects ischemic myocardium. This study was designed to determine whether short-term VS applied before ischemia or at the onset of reperfusion reduces myocardial infarct size (IS), mimicking classic preconditioning and postconditioning. A second objective was to study the participation of muscarinic and nicotinic receptors in the protectionof both preischemic and reperfusion stimulation. FVB mice were subjected to 30 min of regional myocardial ischemia followed by 2 h of reperfusion without VS, with 10 min preischemic VS (pVS), or with VS during the first 10 min of reperfusion (rVS). pVS reduced IS, and this effect was abolished by atropine and wortmannin. rVS also reduced IS in a similar manner and this effect was abolished by the alpha-7 nicotinic acetylcholine receptor (α7nAChR) blocker methyllycaconitine. pVS increased Akt and GSK-3β phosphorylation. No changes inAkt and GSK-3 β phosphorylation were observed in rVS. Stimulation-mediated IS protection was abolished with the JAK-2 blocker AG-490. rVS did not modify IL-6 and IL-10 levels in the plasma or myocardium. Splenic denervation and splenectomy did not abolish the protective effect of rVS. In conclusion, pVS and rVS reduced IS by different mechanisms: pVS activated the Akt/GSK-3β muscarinic pathway, whereas rVS activated α7nAChR and JAK-2, independently of the cholinergic anti-inflammatory pathway.