Vagal stimulation before ischemia or during reperfusion reduces myocardial infarct size in mice

KELLY J; MAZO T; MÉNDEZ DIODATI N; BUCHHOLZ B; GELPI RJ

Buenos Aires

Congreso; International Congress in Translational Medicine ?Cellular and Molecular Pathways as Therapeutic Targets?. International Master Program in Biomedical Sciences.; 2014

International Master Program in Biomedical Sciences

Vagal stimulation (VS) has proven to be beneficial both in myocardial ischemic and reperfusion injury. However the effects and protection mechanisms when stimulation occurs before ischemia or at the beginning of reperfusion are less known. The aim of this study was to determine whether vagal stimulation at the beginning of reperfusion is capable of reducing infarct size in a similar fashion to preischemic stimulation. The second goal was to analyze the possible differences in the involvement of muscarinic and nicotinic cholinergic receptors in the protection due to preischemic stimulation and in the protection due to stimulation during reperfusion. FVB male mice were subjected to: 30 min of regional myocardial ischemia and 2 h of reperfusion without VS (I/R, n=6); with preischemic VS for 10 min (pVS, n=8); with preischemic VS and atropine (pVS+Atr, n=7); with VS during the first 10 min of reperfusion (rVS, n=6); with VS during reperfusion and atropine (rVS+Atr, n=5); with VS during reperfusion and methyllycaconitine (MLA, α7 nicotinic receptor blocker) (rVS+MLA, n=6); with VS during reperfusion and abdominal dorsal vagus nerve section (rVS+DV, n=5); and with VS during reperfusion and splenectomy (rVS+Sp, n=5). The left ventricle was catheterized to assess systolic pressure (LVSP), +dP/dtmax, −dP/dtmax, left ventricle end-diastolic pressure (LVEDP) and heart rate (HR). Subsequently the risk area and infarct size were measured by dyeing with Evans Blue and TTC, respectively. pSV decreased HR by 11% and rSV diminished it by 10%. Both changes were readily reverted by atropine. During ischemia, LVEDP was observed to increase and all LVSP, +dP/dtmax and −dP/dtmax were observed to decrease in all groups without any significant difference between them. VS reduced infarct size when applied previous to the ischemia (43.8±2.9%) or at the beginning of reperfusion (44.0±2.0%), in comparison to the I/R group (60.0±2.9%) (p