# Spinal Neuraxial Modulation of Ventricular Arrhythmias - Mechanisms and Treatment

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $162,540

## Abstract

ABSTRACT
This proposal describes the five-year mentored training program designed to facilitate the career development
of Kimberly Howard-Quijano MD MS into an independent physician-scientist capable of high-level scientific
investigation. Dr. Howard has a long-standing interest in cardiovascular science and a demonstrated
commitment to research. She is currently a junior faculty member in the division of Cardiothoracic
Anesthesiology at the University of California at Los Angeles (UCLA) and has joined the laboratory of Drs. Aman
Mahajan and Yibin Wang, investigating neuraxial modulation of ventricular arrhythmias. Dr. Howard has a strong
background in academic science, completed a Masters of Research at UCLA, and seeks to develop a research
path beginning with mentored investigations into the mechanisms of spinal control of myocardial excitability,
which will lead to an independent research career devoted to investigating neuraxial therapies in treatment of
ventricular arrhythmias.
Sudden cardiac death (SCD) due to ventricular tachyarrhythmias is the leading cause of mortality in the United
States. Neuraxial interventions at the spinal level have been demonstrated to provide an important avenue for
novel therapies aimed at ventricular arrhythmias and SCD. However, the mechanisms through which neuraxial
modulation are affecting myocardial arrhythmogenesis remain to be defined. The objective of this proposal is to
determine how spinal cord processing of cardiac neural impulses controls ventricular excitability after Chronic
MI and to explain how spinal cord stimulation (SCS) therapy works, thus providing a rational basis for optimizing
its efficacy in preventing cardiac dysfunction. The central hypothesis of this proposal is that Chronic MI triggers
pathologic remodeling of cardiospinal neural circuits which increase myocardial sympathoexcitation. SCS
therapy reduces sympathetic output through inhibitory cardioneural pathways (e.g. GABA), reducing ventricular
excitability and arrhythmias after Chronic MI. The proposed studies will use an innovative preclinical model of
Chronic MI which mimics ischemic heart disease in the human condition, to address the current gap in knowledge
regarding the cardiospinal neural interactions that control myocardial sympathoexcitation after Chronic MI. The
results of the proposed studies with acute ischemia in chronic MI hearts (Aim 1), will establish the cardiospinal
neural network through which myocardial excitability is controlled and will reveal important cellular and molecular
mechanisms responsible for the abnormal excitability in the diseased heart. Understanding the spinal neural
pathways, through which ischemia induces myocardial sympathoexcitation, will provide the foundation to define
the neurochemical signaling pathways and molecular mechanisms through which SCS reduces cardiac
arrhythmias (Aim 2). Achievement of these investigations will yield important insights into the mechanisms of
neuromodulation th...

## Key facts

- **NIH application ID:** 10207745
- **Project number:** 5K08HL135418-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kimberly Howard-Quijano
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $162,540
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207745

## Citation

> US National Institutes of Health, RePORTER application 10207745, Spinal Neuraxial Modulation of Ventricular Arrhythmias - Mechanisms and Treatment (5K08HL135418-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10207745. Licensed CC0.

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