Enhancing long-term left ventricular function and mitigating fibrosis in ischemic hearts through pre-ischemic vagus nerve stimulation

FRANCO RIVEROS V; MÉNDEZ DIODATI N; GONZÁLEZ PEÑA B; BERNATENÉ E; BARBIERI I; CICALE E; MORALES C; DONATO M; BUCHHOLZ B

Mar del Plata

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2023

Objective: To evaluate the effectsand mechanisms of brief pre-ischemic electric vagus nerve stimulation (VS) onacute myocardial infarction (MI), and remodeling and function of chronicinfarction with and without reperfusion. Materials and Methods: FVB mice underwent45min regional MI, followed by 2 hours (2hR), or 28 days of reperfusion (28dR),or permanent ischemia (28dI), with or without a 10-min pre-ischemic VS. Leftventricular function (LVF) was assessed via LV catheterization andechocardiography. Histological measurements examined chronic IS and heart remodeling.Results: VS reduction of the acuteIS was blocked by de muscarinic blocker atropine (ATR). VS improved LVF after28dR evidenced by a lower LVEDP(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 did not reverse the positiveeffect of VS on LVF. VS did not affect CSAm (Sham-28d:271±12um;IR-28d:341,3±11um; VS+IR-28d:374,3±20um; p<0.05), but it significantly reducedcollagen ventricular fraction (CVF%) on the infarcted (IA) and non-infarctedareas (n-IA) (IA: IR-28d:45.9±3%; VS+IR-28d:19.6±3.5%; ATR+VS+IR-28d:16.1±1.4;p<0.05 and, n-IA: IR-28d:4.3±0.7%; VS+IR-28d:2.75±0.3%;ATR+VS+IR-28d:1.26±0.2 p<0.05). Moreover, after 28d of MI withoutreperfusion VS improved LVF (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) and reduced CVF% on IA and n-IA(IA: I-28d:82.8±5%; VS+I-28d:64.9±6%; p<0.05 & n-IA:I-28d:3.9±0.7%; VS+I-28d:0.82±0.3%;p<0.05) without changes in neither CSAm nor on the IS. Conclusion: short-term pre-ischemicVS decreased acute IS, improved long-term LVF and extracellular matrixremodeling regardless of infarct size and muscarinic receptors.