Vagal stimulation mimics preconditioning and postconditioning of ischemic myocardium in mice by activating different protection mechanisms

MUÑOZ, MARINA CECILIA; GONZÁLEZ MAGLIO, DANIEL H; BUCHHOLZ, BRUNO; BERNATENÉ, EDUARDO A; DOMINICI, FERNANDO PABLO; KELLY, JAZMIN; MÉNDEZ DIODATI, NAHUEL; GELPI, RICARDO J.; MUÑOZ, MARINA CECILIA; GONZÁLEZ MAGLIO, DANIEL H; BUCHHOLZ, BRUNO; BERNATENÉ, EDUARDO A; DOMINICI, FERNANDO PABLO; KELLY, JAZMIN; MÉNDEZ DIODATI, NAHUEL; GELPI, RICARDO J.

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

AMER PHYSIOLOGICAL SOC

Año: 2018 p. 1289 - 1297

0363-6135

Vagalstimulation (VS) during myocardial ischemia and reperfusion has beneficial effects.However, it is not known whether short-term VS applied prior to ischemia or atthe onset of reperfusion protects ischemic myocardium. This study was designed todetermine whether short-term VS applied before ischemia or at the onset ofreperfusion reduces myocardial infarct size (IS), mimicking classicpreconditioning and postconditioning. A second objective was to study theparticipation of muscarinic and nicotinic receptors in the protection of bothpreischemic and reperfusion stimulation. FVB mice were subjected to 30 min ofregional myocardial ischemia followed by 2 h of reperfusion without VS, with 10min 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 thealpha-7 nicotinic acetylcholine receptor (α7nAChR) blocker methyllycaconitine.pVS increased Akt and GSK-3β phosphorylation. No changes in Akt and GSK-3 βphosphorylation were observed in rVS. Stimulation-mediated IS protection wasabolished with the JAK-2 blocker AG-490. rVS did not modify IL-6 and IL-10levels in the plasma or myocardium. Splenic denervation and splenectomy did notabolish the protective effect of rVS. In conclusion, pVS and rVS reduced IS bydifferent mechanisms: pVS activated the Akt/GSK-3β muscarinic pathway, whereasrVS activated α7nAChR and JAK-2, independently of the cholinergicanti-inflammatory pathway.