Structural and function organization of intrathoracic extracardiac autonomic projections to the porcine heart: Implications for targeted neuromodulation therapy.


Journal

Heart rhythm
ISSN: 1556-3871
Titre abrégé: Heart Rhythm
Pays: United States
ID NLM: 101200317

Informations de publication

Date de publication:
06 2022
Historique:
received: 23 06 2021
revised: 20 01 2022
accepted: 28 01 2022
pubmed: 7 2 2022
medline: 3 6 2022
entrez: 6 2 2022
Statut: ppublish

Résumé

Mapping the structure/function organization of the cardiac nervous system is foundational for implementation of targeted neuromodulation-based therapeutics for the treatment of cardiac disease. The purpose of this study was to define the spatial organization of intrathoracic parasympathetic and sympathetic efferent projections to the heart. Yucatan mini-pigs (N = 11) were anesthetized and the thoracic cavity exposed. Electrical stimulation of the cervical vagi and stellate ganglia was performed individually, and hemodynamic responses were assessed in the intact state and after progressive debranching of each thoracic vagosympathetic trunk (VST). Subsequently, residual cardiac efferent projections arising from paravertebral chain ganglia (T1-T4) were evaluated by stimulation before and after individual ganglionic debranching. Stimulation of the cervical vagi decreased heart rate and contractility while prolonging the activation-recovery interval (ARI). Stimulation of the stellate ganglia increased heart rate and contractility and decreased ARI. The majority of parasympathetic and sympathetic cardiac-evoked responses were mitigated after debranching of the right VST rostral to heart, whereas the left VST demonstrated a distribution with greater dispersion and caudal intrathoracic shift compared to the right. After complete thoracic VST debranching, stimulation of the T4 paravertebral chain ganglia demonstrated residual cardiac sympathetic efferent innervation to the heart in ∼50% of animals. That response was mitigated by transecting medial ganglionic branches. The nexus point for optimum neuromodulation engagement of parasympathetic efferent projections to the heart is the cervical vagus and the T1-T2 paravertebral chain ganglia for sympathetic control. Removal of principal sympathetic efferent projections to heart requires targeting the T1-T4 regions of the paravertebral chain.

Sections du résumé

BACKGROUND
Mapping the structure/function organization of the cardiac nervous system is foundational for implementation of targeted neuromodulation-based therapeutics for the treatment of cardiac disease.
OBJECTIVE
The purpose of this study was to define the spatial organization of intrathoracic parasympathetic and sympathetic efferent projections to the heart.
METHODS
Yucatan mini-pigs (N = 11) were anesthetized and the thoracic cavity exposed. Electrical stimulation of the cervical vagi and stellate ganglia was performed individually, and hemodynamic responses were assessed in the intact state and after progressive debranching of each thoracic vagosympathetic trunk (VST). Subsequently, residual cardiac efferent projections arising from paravertebral chain ganglia (T1-T4) were evaluated by stimulation before and after individual ganglionic debranching.
RESULTS
Stimulation of the cervical vagi decreased heart rate and contractility while prolonging the activation-recovery interval (ARI). Stimulation of the stellate ganglia increased heart rate and contractility and decreased ARI. The majority of parasympathetic and sympathetic cardiac-evoked responses were mitigated after debranching of the right VST rostral to heart, whereas the left VST demonstrated a distribution with greater dispersion and caudal intrathoracic shift compared to the right. After complete thoracic VST debranching, stimulation of the T4 paravertebral chain ganglia demonstrated residual cardiac sympathetic efferent innervation to the heart in ∼50% of animals. That response was mitigated by transecting medial ganglionic branches.
CONCLUSION
The nexus point for optimum neuromodulation engagement of parasympathetic efferent projections to the heart is the cervical vagus and the T1-T2 paravertebral chain ganglia for sympathetic control. Removal of principal sympathetic efferent projections to heart requires targeting the T1-T4 regions of the paravertebral chain.

Identifiants

pubmed: 35124232
pii: S1547-5271(22)00107-2
doi: 10.1016/j.hrthm.2022.01.033
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

975-983

Subventions

Organisme : NIBIB NIH HHS
ID : U01 EB025138
Pays : United States
Organisme : NIH HHS
ID : OT2 OD023848
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Auteurs

Michael Dacey (M)

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, California; UCLA Molecular, Cellular & Integrative Physiology Program, UCLA, Los Angeles, California.

Owais Salahudeen (O)

Department of Ecology and Evolutionary Biology, UCLA, Los Angeles, California.

Mohammed A Swid (MA)

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, California.

Cameron Carlson (C)

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, California.

Kalyanam Shivkumar (K)

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, California; UCLA Molecular, Cellular & Integrative Physiology Program, UCLA, Los Angeles, California.

Jeffrey L Ardell (JL)

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, California; UCLA Molecular, Cellular & Integrative Physiology Program, UCLA, Los Angeles, California. Electronic address: jardell@mednet.ucla.edu.

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Classifications MeSH