Non-invasive tragus stimulation improves cardiac post-ischemic remodeling by regulating cardiac parasympathetic activity

ESC Heart Fail. 2022 Dec;9(6):4129-4138. doi: 10.1002/ehf2.14146. Epub 2022 Sep 9.

Abstract

Aims: Our previous study proved that low-level tragus nerve stimulation (LL-TS) could improve left ventricular remodelling by cardiac down-stream mechanisms. However, the cardiac up-stream mechanisms remain unknown.

Methods and results: Twenty-eight adult beagle dogs were randomly divided into an MI group (myocardial infarction was induced by permanent ligation of the left coronary artery, n = 10), an LL-TS group (MI plus intermittent LL-TS treatment, n = 10), and a control group (sham ligation with the same stimulation as the LL-TS group, n = 8). Auricular tragus nerve was bilaterally delivered to the tragus via ear-clips connected to a custom-made stimulator. The voltage slowing sinus rate was used as the threshold to set the LL-TS 80% below this level. At the end of 4 weeks post-MI, LL-TS could significantly increase atrial ganglion plex (GP) activity, decreased left stellate ganglion (LSG) activity, reduced LV dilation, and improved ventricular functions. Chronic intermittent LL-TS treatment significantly attenuated left ventricular remodelling via the up-regulation of α7nAChR expression and the down-regulation of MMP-9 level in post-MI LV tissue. The elevated protein and mRNA of MMP-9 levels in remote areas were significantly ameliorated by LL-TS treatment.

Conclusions: Chronic LL-TS increased GP neural activity and improved ventricular remodelling possibly via α7nAChR/MMP-9 axis.

Keywords: Matrix metallopeptidase 9; Tragus nerve stimulation; Ventricular remodelling; α7 nicotinic acetylcholine receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dogs
  • Heart Atria
  • Matrix Metalloproteinase 9* / metabolism
  • Myocardial Infarction* / metabolism
  • Ventricular Remodeling / physiology
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • alpha7 Nicotinic Acetylcholine Receptor
  • Matrix Metalloproteinase 9