Chronic intermittent low-level transcutaneous electrical stimulation of auricular branch of vagus nerve improves left ventricular remodeling in conscious dogs with healed myocardial infarction.

Abstract

Vagus nerve stimulation attenuates left ventricular (LV) remodeling after myocardial infarction (MI). Our previous study found a noninvasive approach to deliver vagus nerve stimulation by transcutaneous electric stimulation of auricular branch of vagus nerve. So we hypothesize that chronic intermittent low-level tragus stimulation (LL-TS) could attenuate LV remodeling in conscious dogs with healed MI. Thirty beagle dogs were randomly divided into 3 groups, MI group (left anterior descending artery and major diagonal branches ligation to introduce MI, n=10), LL-TS group (MI plus chronic intermittent LL-TS, n=10), and control group (sham surgery without stimulation, n=10). Tragus stimulation was delivered to bilateral tragus with ear-clips connected to a custom-made stimulator. The voltage slowing sinus rate was used as the threshold for setting LL-TS at 80% below that. LL-TS group was given 4 hours stimulation at 7-9 am and 4-6 pm on conscious dogs. At the end of 90-day follow-up, LL-TS group significantly reduced LA and LV dilatation, improved LV contractile and diastolic function, reduced infarct size by ≈50% compared with MI group. LL-TS treatment alleviated cardiac fibrosis and significantly decreased protein expression level of collagen I, collagen III, transforming growth factor β1, and matrix metallopeptidase 9 in LV tissues. The plasma level of high-specific C-reactive protein, norepinephrine, N-terminal pro-B-type-natriuretic peptide in LL-TS group was significantly lower than those in MI group from the 7th day to the end of follow-up. Chronic intermittent low-level transcutaneous electric stimulation of auricular branch of vagus nerve can attenuate LV remodeling in conscious dogs with healed MI.