Sympathetic hyperactivity abolishes the myocardial protective effect of vagal stimulation in mice with cardiac gsα overexpression

KELLY J; MÉNDEZ DIODATI, NAHUEL; BERNATENÉ E; CASANOVA V; BUCHHOLZ B; GELPI RJ

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Although important myocardial protective effects of vagal stimulation(VS) have been demonstrated experimentally, the clinical results arenot entirely conclusive. We hypothesized that the dysautonomia thataccompanies heart disease may interfere with myocardial protection.The objective was to study whether sympathetic cardiac hyperactivityabolishes the protective effects of classical preconditioningand preconditioning mimicked by VS in transgenic mice with cardiacoverexpression of GSα protein.Transgenic FVB mice with specific cardiac overexpression of theGSα protein (TG) and their respective non-transgenic controls (WT)were subjected to 30 min of regional ischemia and 2 hours of reperfusion(I/R). Both TG and WT mice received VS for 10 min beforeischemia or 3 preconditioning cycles for 5 min of ischemia and 5min of myocardial reperfusion (PC) before prolonged ischemia (n=5-7 per group). All animals were catheterized to measure ventricularfunction. Hearts were dyed with Evans Blue and incubated in TTC tomeasure the infarct size (IS).The heart rate (HR) of the WT and TG mice was 438±11 and 664±14(p<0.05), respectively. VS reduced HR by 10% in WT animals(p<0.05 vs basal), and only by 6% in TG mice (p=NS vs basal). TheVS and the PC significantly reduced the IS with respect to the controlgroup in the WT groups (I/R-WT: 56±2%, VS-WT: 44±3%, PCWT:35±2%) (p<0.05). The IS of the I/R-TG group was similar to thenon-transgenic group (I/R-TG: 57±5%, p=NS vs I/R-WT). However,in the TG animals the protection of VS (55±5.0%) and PC (52±2.0%)was lost (p=NS vs I/R-TG).In conclusion, preischemic VS reduced infarct size to a similar degreeto ischemic PC. This protective effect of VS and PC was notobserved in TG mice with cardiac sympathetic overactivity due tooverexpression of GSα protein.