# Peripheral Sympathetic Dysfunction in Cardiac Disease

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $768,349

## Abstract

Project Summary
Myocardial infarction and heart failure increase risk for ventricular arrhythmias and sudden cardiac death.
Autonomic dysregulation and sympathetic hyperactivity accompany these diseases and trigger lethal
arrhythmias. Interventions that target the central nervous system to inhibit sympathetic outflow have not been
effective in patients, but interventions that target the peripheral sympathetic nervous system decrease
arrhythmias and prolong life. We hypothesize that central nervous system activity is amplified by post-
ganglionic neurons in cardiovascular disease to enhance norepinephrine and neuropeptide Y release at the
heart, which contributes to pathology. We have discovered excitatory collaterals between sympathetic post-
ganglionic neurons that foster synchronous amplification of preganglionic signals. We hypothesize that
disease-induced changes in the heart trigger morphological and electrical transformation of sympathetic
postganglionic neurons that results in sympathetic hyperactivity. To identify the mechanisms responsible for
hyper-sympathetic changes, we exploit transgenic mouse models coupled with neurochemistry, single cell
RNAseq, patch clamp electrophysiology, retrograde tracing and 3D reconstruction of labeled neurons to link
structure with function. We will connect neural function to norepinephrine and neuropeptide Y release in the
heart. The combined power of single cell synaptic measures with mouse genetics and retrograde tracing offers
unique opportunities to resolve mechanisms responsible for augmented transmission specific to cardiac
projecting neurons. We will test the hypotheses that myocardial infarction and heart failure drive increased
cardiac sympathetic transmission: through expanding dendritic arbors and their synaptic inputs (Aim 1);
through enhancing neuronal activity (Aim 2); and through altering neuronal calcium handling (Aim 3). We have
assembled a unique team of accomplished experts, key animal models, and powerful genetic tools to
accomplish these studies. We expect that novel insights and targets for therapeutic intervention will come from
the studies described here, and that this work with have implications for treatment of the many diseases
characterized by high sympathetic activation.

## Key facts

- **NIH application ID:** 10133133
- **Project number:** 5R01HL146833-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** BETH A HABECKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $768,349
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133133

## Citation

> US National Institutes of Health, RePORTER application 10133133, Peripheral Sympathetic Dysfunction in Cardiac Disease (5R01HL146833-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133133. Licensed CC0.

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