INVESTIGADORES
BUCHHOLZ Bruno
congresos y reuniones científicas
Título:
Vagal stimulation before ischemia or during reperfusion reduces myocardial infarct size in mice
Autor/es:
KELLY J; MAZO T; MÉNDEZ DIODATI N; BUCHHOLZ B; GELPI RJ
Lugar:
Buenos Aires
Reunión:
Congreso; International Congress in Translational Medicine ?Cellular and Molecular Pathways as Therapeutic Targets?. International Master Program in Biomedical Sciences.; 2014
Institución organizadora:
International Master Program in Biomedical Sciences
Resumen:
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<0.05). Atropine successfully
reverted the protective effect of preischemic VS (54.6±1.1%), although it
failed to revert the protection of VS during reperfusion (40.6±2.8%). The
reduction of infarct size due to stimulation during reperfusión was prevented
by MLA (59.7±2.8%), yet it was not reverted by dorsal vagal section (43.0±3.8%)
nor splenectomy (43.4±3.5%). To conclude, VS during reperfusion reduces infarct
size in a similar fashion to preischemic VS. Preischemic protection relies on
the muscarinic pathway and protection in reperfusion is dependent on the α7
nicotinic pathway, yet independent of parasympathetic splenic innervation.