# Mechanistic refinement of non-invasive autonomic neuromodulation for cardiac arrhythmia

> **NIH NIH K23** · UNIVERSITY OF PENNSYLVANIA · 2022 · $173,340

## Abstract

The autonomic nervous system has an important role in the pathogenesis of cardiac arrhythmias thus
providing a critical opportunity for therapeutic intervention. Modulation of the autonomic nervous system
has been attempted through numerous means including surgical sympathectomy, catheter-based
ablation procedures, and transcutaneous approaches. Although autonomic innervation has been shown
to have a significant effect on arrhythmogenicity, the complex network of interactions and the optimal
strategies for interrupting this network are inadequately characterized. To further the field, this research
will integrate established principles and techniques from neuroscience to study the role of autonomic
neuromodulation in the treatment of cardiac arrhythmias. The investigation will focus on the ability of
repetitive transcutaneous magnetic stimulation (TcMS) to modulate synaptic strength of autonomic
cardiac innervation. The feasibility of this non-destructive and non-invasive technology is supported by
Dr. Markman’s recent work published in JAMA targeting the cervical sympathetic chain with an inhibitory
TcMS protocol in patients with ventricular tachycardia (VT) storm. The proposed research plan aims to
improve understanding of the cardiac effects of autonomic neuromodulation, and to assess the efficacy
of TcMS in patients with VT storm. Aim 1 seeks to characterize the cardiac electrophysiological effects
of autonomic neuromodulation by invasively measuring conduction properties as well as levels of
catecholamines and inflammatory cytokines before and after neuromodulation. This will develop critical
tools for characterizing neural-cardiac interactions, allowing definitive assessment of their complex
relationship.
Aim 2 seeks to characterize the cardiac electrophysiological effects of autonomic neuromodulation by
invasively measuring conduction properties as well as levels of catecholamines and inflammatory
cytokines before and after neuromodulation. In combination, the findings from these aims will yield critical
information regarding the mechanistic characterization of complex cardiac-neural pathways and help
establish the role of a novel method of neuromodulation. In addition, this research will promote critically
important continued interdisciplinary collaboration between neuroscientists and cardiovascular medicine.
Dr. Markman, an early career investigator and a fellow in cardiac electrophysiology, has a long-term goal
of establishing an independent research program in autonomic neuromodulation focused on
mechanistically defining the complex neural circuits involved in cardiac arrhythmias. These research aims
are part of a comprehensive training plan and will be supervised by a mentorship and advisory team
consisting of national leaders in arrhythmia and neuroscience research and will guide his transition to an
independently funded research career.

## Key facts

- **NIH application ID:** 10525948
- **Project number:** 1K23HL161349-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Timothy Markman
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $173,340
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525948

## Citation

> US National Institutes of Health, RePORTER application 10525948, Mechanistic refinement of non-invasive autonomic neuromodulation for cardiac arrhythmia (1K23HL161349-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10525948. Licensed CC0.

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