# Antiarrhythmic mechanisms of chronic vagal nerve stimulation in sympathetic neurons

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $40,828

## Abstract

PROJECT SUMMARY/ABSTRACT
Ventricular tachycardia/fibrillation (VT/VF) occur after myocardial infarction (MI), and are a common cause of
sudden cardiac death. Sympathovagal imbalance, resulting from structural and functional remodeling of
cardiac sympathetic neurons, promotes the initiation of VT/VF after MI. This process remains poorly
understood, and current drugs that prevent sympathetic excess are limited by significant side effects and
inadequate efficacy. Vagal nerve stimulation (VNS) is a promising therapy to restore sympathovagal balance
with supporting data from animal models and humans, but the mechanisms underlying its benefits are poorly
understood. The goal of this proposal is to test the novel hypothesis that chronic VNS exerts its protective
effects against VT/VF and progressive cardiac dysfunction primarily by impacting sympathetic neuronal
dysfunction after MI.
 In preliminary studies, we have shown that sympathetic dysfunction encompasses several key
elements that include neuronal dysfunction, satellite glial activation, neuroinflammation and aberrant
spatiotemporal neural activity within sympathetic ganglia such as stellate ganglia. Pilot studies from our group
show that VNS exerts a governing effect on sympathetic function acutely, independent on the level of
sympathoexcitation, and chronically mitigates arrhythmogenesis following MI. We will test our hypotheses
using novel tools from a multidisciplinary team of investigators in 3 specific aims in pigs with chronic MI. We
will delineate the impact of chronic VNS on structural and neurochemical remodeling in sympathetic neurons
(Aim 1). We will determine whether chronic VNS, with its anti-inflammatory effects, attenuates satellite glial
activation and neuroinflammation in stellate ganglia (Aim 2). Finally, we will dissect the impact of chronic VNS
on spatiotemporal activity of stellate ganglion neurons using novel computational tools applied to high-
resolution high-fidelity in vivo extracellular neural recordings from the stellate ganglion (Aim 3). We will directly
link the neuroanatomical (Aim 1), neuroinflammatory (Aim 2), and neurophysiologic (Aim 3) remodeling to
spontaneous and inducible VT/VF, as well as proarrhythmic local myocardial arrhythmogenic mechanisms.
The results of this proposal will 1) advance our understanding of the mechanistic underpinnings of VNS
efficacy and 2) potentially uncover novel pathways by which sympathetic dysfunction can be prevented or
reversed, to which new therapeutic strategies can be devised.

## Key facts

- **NIH application ID:** 10635151
- **Project number:** 1R01HL167885-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Olujimi A Ajijola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $40,828
- **Award type:** 1
- **Project period:** 2023-05-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10635151

## Citation

> US National Institutes of Health, RePORTER application 10635151, Antiarrhythmic mechanisms of chronic vagal nerve stimulation in sympathetic neurons (1R01HL167885-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10635151. Licensed CC0.

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