Chronic Intermittent Low-Level Stimulation of Tragus Reduces Cardiac Autonomic Remodeling and Ventricular Arrhythmia Inducibility in a Post-Infarction Canine Model

Lilei Yu; Songyun Wang; Xiaoya Zhou; Zhuo Wang; Bing Huang; Kai Liao; Gaowa Saren; Mingxian Chen; Sunny S Po; Hong Jiang

doi:10.1016/j.jacep.2015.11.006

Chronic Intermittent Low-Level Stimulation of Tragus Reduces Cardiac Autonomic Remodeling and Ventricular Arrhythmia Inducibility in a Post-Infarction Canine Model

JACC Clin Electrophysiol. 2016 Jun;2(3):330-339. doi: 10.1016/j.jacep.2015.11.006. Epub 2015 Dec 9.

Authors

Lilei Yu¹, Songyun Wang¹, Xiaoya Zhou¹, Zhuo Wang¹, Bing Huang¹, Kai Liao¹, Gaowa Saren¹, Mingxian Chen², Sunny S Po³, Hong Jiang⁴

Affiliations

¹ Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
² Department of Cardiology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
³ Heart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. Electronic address: sunny-po@ouhsc.edu.
⁴ Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address: whujianghong@163.com.

PMID: 29766893
DOI: 10.1016/j.jacep.2015.11.006

Abstract

Objectives: This study investigated whether chronic low-level tragus stimulation (LL-TS) inhibits cardiac sympathetic remodeling and reduces ventricular arrhythmia inducibility in a post-infarction canine model.

Background: Low-level vagal stimulation has been shown to suppress cardiac sympathetic activity, which plays an important role in ventricular arrhythmia after myocardial infarction (MI). Our previous studies reported a noninvasive approach to deliver vagal stimulation by transcutaneous stimulation at the tragus, where the auricular branch of the vagus nerve is located.

Methods: Twenty-two beagles were randomized to the normal control (n = 6), MI (left anterior descending coronary artery ligation without LL-TS [n = 8]), and TS (MI plus LL-TS [n = 8]) groups. LL-TS was delivered 2 h each day at 80% below the threshold which slowed sinus rate.

Results: At 2-month follow-up, LL-TS was found to significantly reduce ventricular arrhythmia inducibility (arrhythmia score: 1.8 ± 0.8 vs. 3.6 ± 0.7, p < 0.01, compared to the MI group), decreased left stellate ganglion (LSG) activity (frequency: 32 ± 15 vs. 112 ± 29 impulses/s; and amplitude: 0.15 ± 0.12 mV vs. 0.38 ± 0.12 mV, compared to MI group), and attenuated cardiac sympathetic remodeling induced by chronic MI. The nerve growth factor (NGF) protein was down-regulated, whereas the small conductance calcium-activated potassium channel type2 (SK2) protein was up-regulated in the LSG by chronic LL-TS.

Conclusions: Chronic LL-TS could reduce the ventricular arrhythmia inducibility, LSG neural activity and sympathetic neural remodeling in a post-infarction canine model. Down-regulation of NGF protein and up-regulation of SK2 protein in the LSG contribute to the salutary effects of LL-TS.

Keywords: left stellate ganglion; neural remodeling; tragus stimulation; ventricular arrhythmia.