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

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 alpha 7nAChR 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 alpha 7nAChR/MMP-9 axis.