Pre-ischemic vagus nerve stimulation improves long-term left ventricular function and reduces fibrosis in ischemic hearts with or without reperfusion

VERENA FRANCO RIVEROS; NAHUEL MÉNDEZ DIODATI; EDUARDO BERNATENÉ; BEATRIZ GONZÁLEZ PEÑA; IGNACIO BARBIERI; ELIANA CICALE; VERÓNICA CASANOVA; CELINA MORALES; MARTÍN DONATO; RICARDO J. GELPI; BRUNO BUCHHOLZ

Mar del Plata

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2022

Sociedad Argentina de Investigación Clínica

The aim was to determine the effects of brief electric vagus nervestimulation (VS) applied before ischemia on acute myocardial infarction (MI)and its long-term benefits on an experimental ischemia-reperfusion andnon-reperfusion model. Mice underwent regional MI for 45min, followed by either2 hours (2hR) or 28 days of reperfusion (28dR), with or without 10min ofpre-ischemic VS. LVF was assessed by catheterization through the right carotidartery and, by echocardiography: EF, SF, IVRT. Participation of muscarinicreceptors (MR) was determined by the administration of atropine (ATR) duringVS. Infarct size (IS) was measured by TTC stain on acute groups. Histologicalmeasurements were also assessed to study myocardial IS and remodeling. VS decreasedIS after 2hR, from 65.3±1.7% to 43±2.1% (p<0.05) and ATR reversed the protection(IS:60.4±1.6%; p<0.001 vs VS+IR-2h). VS improved LVF after 28dR evidenced bya lower LVPDF(mmHg) (Sham-28d:3.8±0.2; IR-28d:6.8±0.5; VS+IR-28d:3.7±1; p<0.01),higher EF% (Sham-28d:77.3±11.7%; IR-28d:59.7±2.8%; VS+IR-28d:69.6±2.4%;p<0.05), and lower TRIV (Sham-28d:19.4±1.4; IR-28d:30.3±1.2;VS+IR-28d:25±0.9; p<0.05). ATR didn’t reverse VS protective effects on LVF.VS didn’t reduce CSAm (Sham-28d:267.5±9um; IR-28d:380,1±34um;VS+IR-28d:374,3±25um; p<0.05), but collagen ventricular fraction (CVF%) on theinfarcted (IA) and non-infarcted area (n-IA) was significantly reduced (IA: IR-28d:37.6±6,5%;VS+IR-28d:19.7±3,5%; ATR+VS+IR-28d:16.1±1,4; p<0.05 and, n-IA: IR-28d:5.9±1,7%;VS+IR-28d:2.75±1,4%; ATR+VS+IR-28d:1.26±0,3 p<0.05). Likewise, VS improvedLVF after 28d of MI without R (LVDP: I28d:8.4±1mmHg; VS+I28d:3.1±0.8;p<0.05; EF%:I28d: 50.6±4; VS+I28d:69.5±1; p<0.05). VS reduced neitherCSAm, nor CVF% on no-reperfusion protocols. In conclusion, short-termpre-ischemic VS reduces acute IS, improves long-term LVF, and reduces fibrosisin ischemic hearts with or without R independently of MR’s action or IS.