BENEFICIAL ROLE OF PRE-ISCHEMIC VAGAL STIMULATION ON REGIONAL MYOCARDIAL ISCHEMIA WITH OR WITHOUT REPERFUSION

VERENA FRANCO RIVEROS; NAHUEL MÉNDEZ DIODATI; CELINA MORALES; EDUARDO BERNATENÉ; MARTÍN DONATO; RICARDO J. GELPI; BRUNO BUCHHOLZ

Congreso; International Society for Heart Research- Latin America Section. Online event; 2021

IntroductionWehave previously proven that vagal stimulation (VS) decreases infarct size (IS)when applied before ischemia, thus mimicking classic preconditioning, yetwithout improving left ventricular function (LVF). Nonetheless, it is stillunknown whether VS effects can ameliorate the chronic evolution of myocardialinfarction, by improving left ventricular remodeling or function.ObjectiveOur goal was to analyze the effects of brief VS applied before ischemia on acutemyocardial infarction and its long-term benefits on an experimentalischemia-reperfusion and non-reperfusion model.Methods We performed a regional myocardial ischemia via ligation of the left descending      coronary artery on male FVB mice during 45 min, followed by either 2 hours (2hR) or 28 days of reperfusion (28dR) or no reperfusion at all,with or without 10 min of pre-ischemic VS. LVF was assessed by catheterization of the left ventricle throughthe right carotid artery and by echocardiography. Morphometric parameters werealso analyzed by comparing the following indices of each group: weight of both ventricles (VW) and the lungs (LW) each divided by the lengths of the tail (TL) and tibia (TiL). Lastly, IS was measured by TTC stain on the 2hR groups. Myocardial remodelingwas assessed by histology in the 28dR group. Animal Care Committee,University of Buenos Aires, approved protocol no.339/18. Results  IS measured after 2h of rep.significantly decreased with VS, from 65.3±1.7% to 43±2.1% (p<0.05) andatropine reversed this protection (IS: 60.4±1.6%; p<0.001 vs VS+IR-2h). VSimproved LVF after 28 days of rep. evidenced by a lower LVPDF (Sham-28d:3.8±0.2 mmHg; IR-28d: 6.8±0.5 mmHg; VS+IR-28d: 3.7±1 mmHg; p<0.01), higherEF% (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). Likewise, VS improved LVF after 28 days of myocardial infarctionwithout rep. (LVDP: I28d: 8.4±1 mmHg; VS+I28d: 3.1±0.8; p<0.05; EF%: I28d:50.6±4; VS+I28d: 69.5±1; p<0.05). AlthoughVS was able to improve LVF in myocardial infarctions with or without rep., itdid not modified neither the normalized biventricular weight, nor myocytes’cross-sectional area. Conclusions BriefVS applied before ischemia reduces acute infarct sizeand improves long-term LVF in ischemic hearts with or withoutreperfusion independently of muscarinic receptors’ action or infarct size.