Mimicking Preconditioning by Vagal Stimulation. Effects on Ventricular Function in a Chronic Experimental Model

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Abstract

Background: Previous studies have shown that preischemic vagal electrostimulation (pVS) reduces acute myocardial infarct size,without a significant improvement on ventricular function within the two-hour reperfusion period. It is unknown which are thelong-term effects of pVS on left ventricular function (LVF).

Objectives: The aim of this study was to analyze whether the protective effects of brief pVS on acute infarct size improves LVF in a chronic myocardial ischemia-reperfusion model.

Methods: FVB mice were subjected to 45-minute regional myocardial ischemia followed by 2 hours of reperfusion or 28-day postreperfusion follow-up with or without 10-minute pVS. Infarct size (IS) was measured with 2,3,5-triphenyltetrazolium chloride, and LVF was assessed by echocardiography and left ventricular catheterization.

Results: Preischemic vagal stimulation reduced IS from 66.8±3.2% to 43.2±1.6% (p <0.001) at 2 hours of reperfusion, without a favorable LVF response. At 28 days, the pVS group exhibited LVF improvement, with lower left ventricular end-diastolic pressure(4.44±1 vs. 6.91±1 mmHg in the control group; p<0.05), higher ejection fraction (69.7±2.8% vs. 59.3±3.2; p<0.05), greater shortening fraction (33.4±2.23 vs. 25.8±1.8%; p<0.05) and lower isovolumic relaxation time (25±0.8 ms vs. 30.3±1.2 ms; p<0.05)

Conclusions: In a mice model of myocardial ischemia and reperfusion, mimicking ischemic preconditioning by VS improves the chronic outcome of infarction, resulting in greater LVF recovery.