# Long-Term Stimulation of the Left Dorsal Branch of the Thoracic Nerve Improves Ventricular Electrical Remodeling in a Canine Model of Chronic Myocardial Infarction

## TL;DR

Stimulating a specific thoracic nerve in dogs with heart damage improves heart electrical function by reducing nerve activity and preventing cell death signaling.

## Contribution

This study demonstrates that long-term stimulation of the left dorsal thoracic nerve reduces ventricular electrical remodeling in a canine model of chronic heart attack.

## Key findings

- LDTN stimulation reversed abnormal heart rate variability in MI dogs.
- Stimulation reduced dispersion of electrical activity and increased ventricular fibrillation threshold.
- LDTN suppressed Wnt/β-catenin signaling and promoted sympathetic nerve cell death.

## Abstract

To evaluate the ventricular electrophysiologic effects of long-term stimulation of the left dorsal branch of thoracic nerve (LDTN) derived from the left stellate ganglion (LSG) in a canine model of chronic myocardial infarction (MI).

Seventeen adult male beagles were randomly divided into three groups: the sham group (sham operated, n = 6), the MI group (n = 6), and the MI + LDTN group (MI plus LDTN stimulation, n = 5). The canine model of chronic MI was induced by the occlusion of the left anterior descending artery (LADO). The LDTN was separated and intermittently stimulated immediately after LADO for 2 months. The heart rate variability (HRV) analysis, in vivo electrophysiology, the evaluation of LSG function and neural activity, histological staining, and western blotting (WB) assay were performed to evaluate the effect of LDTN stimulation on the heart.

The canine MI model was successfully established by LADO, and the LDTN was separated and stimulated immediately after LADO. The HRV analysis showed that LDTN stimulation reversed the increased LF value and LF/HF ratio of the MI group. LDTN stimulation prolonged the shortening ERP and APD90, decreased the dispersion of ERP and APD90, and increased the VFT. Additionally, LDTN stimulation inhibits the LSG function and neural activity. Furthermore, LDTN stimulation suppressed the activation of Wnt/β-catenin signaling, which contributed to the LSG neuronal apoptosis by upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2.

LDTN stimulation could attenuate cardiac sympathetic remodeling and improve ventricular electrical remodeling, which may be mediated by suppressing the activated Wnt/β-catenin signaling pathway and then promoting the LSG neuronal apoptosis.