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

    Dacey, Michael / Salahudeen, Owais / Swid, Mohammed A / Carlson, Cameron / Shivkumar, Kalyanam / Ardell, Jeffrey L

    Heart rhythm

    2022  Volume 19, Issue 6, Page(s) 975–983

    Abstract: 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 ...

    Abstract 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.
    MeSH term(s) Animals ; Autonomic Nervous System/physiology ; Electric Stimulation ; Heart/innervation ; Stellate Ganglion ; Swine ; Swine, Miniature ; Sympathetic Nervous System/physiology ; Vagus Nerve/physiology
    Language English
    Publishing date 2022-02-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2229357-7
    ISSN 1556-3871 ; 1547-5271
    ISSN (online) 1556-3871
    ISSN 1547-5271
    DOI 10.1016/j.hrthm.2022.01.033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Thoracic epidural blockade after myocardial infarction benefits from anti-arrhythmic pathways mediated in part by parasympathetic modulation.

    Hoang, Jonathan D / van Weperen, Valerie Yh / Kang, Ki-Woon / Jani, Neil R / Swid, Mohammed A / Chan, Christopher A / Lokhandwala, Zulfiqar Ali / Lux, Robert L / Vaseghi, Marmar

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Background: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachyarrhythmias (VT) in small case-series of patients with refractory VT and cardiomyopathy. However, its electrophysiological and autonomic effects in ... ...

    Abstract Background: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachyarrhythmias (VT) in small case-series of patients with refractory VT and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear and its use after myocardial infarction (MI) is limited by concerns for potential RV dysfunction.
    Methods: MI was created in Yorkshire pigs (
    Results: TEA reduced inducibility of VT/VF by 70%. TEA did not affect RV-systolic pressure or contractility, although LV-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular ERPs prolonged significantly at critical sites of arrhythmogenesis, and S
    Conclusion: TEA does not compromise RV function in infarcted hearts. Its anti-arrhythmic mechanisms are mediated by increases in ventricular ERP and ARIs, decreases in S
    Abstract illustration: Myocardial infarction is known to cause cardiac autonomic dysfunction characterized by sympathoexcitation coupled with reduced vagal tone. This pathological remodeling collectively predisposes to ventricular arrhythmia. Thoracic epidural anesthesia not only blocks central efferent sympathetic outflow, but by also blocking ascending projections of sympathetic afferents, relieving central inhibition of vagal function. These complementary autonomic effects of thoracic epidural anesthesia may thus restore autonomic balance, thereby improving ventricular electrical stability and suppressing arrhythmogenesis. DRG=dorsal root ganglion, SG=stellate ganglion.
    Language English
    Publishing date 2024-03-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.14.585127
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Scalable and reversible axonal neuromodulation of the sympathetic chain for cardiac control.

    Hadaya, Joseph / Buckley, Una / Gurel, Nil Z / Chan, Christopher A / Swid, Mohammed A / Bhadra, Niloy / Vrabec, Tina L / Hoang, Jonathan D / Smith, Corey / Shivkumar, Kalyanam / Ardell, Jeffrey L

    American journal of physiology. Heart and circulatory physiology

    2021  Volume 322, Issue 1, Page(s) H105–H115

    Abstract: Maladaptation of the sympathetic nervous system contributes to the progression of cardiovascular disease and risk for sudden cardiac death, the leading cause of mortality worldwide. Axonal modulation therapy (AMT) directed at the paravertebral chain ... ...

    Abstract Maladaptation of the sympathetic nervous system contributes to the progression of cardiovascular disease and risk for sudden cardiac death, the leading cause of mortality worldwide. Axonal modulation therapy (AMT) directed at the paravertebral chain blocks sympathetic efferent outflow to the heart and maybe a promising strategy to mitigate excess disease-associated sympathoexcitation. The present work evaluates AMT, directed at the sympathetic chain, in blocking sympathoexcitation using a porcine model. In anesthetized porcine (
    MeSH term(s) Animals ; Axons/metabolism ; Axons/physiology ; Catecholamines/metabolism ; Electric Stimulation ; Female ; Heart/innervation ; Heart/physiology ; Heart Rate ; Male ; Myocardial Contraction ; Norepinephrine/metabolism ; Swine ; Sympathetic Nervous System/metabolism ; Sympathetic Nervous System/physiology ; Synaptic Transmission
    Chemical Substances Catecholamines ; Norepinephrine (X4W3ENH1CV)
    Language English
    Publishing date 2021-12-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00568.2021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Aorticorenal ganglion as a novel target for renal neuromodulation.

    Hori, Yuichi / Temma, Taro / Wooten, Christian / Sobowale, Christopher / Tahmasian, Sarah / Chan, Christopher / Swid, Mohammed A / Zuckerman, Jonathan E / Peacock, Warwick / Ajijola, Olujimi A

    Heart rhythm

    2021  Volume 18, Issue 10, Page(s) 1745–1757

    Abstract: Background: Clinical trials for renal artery (RA) ablation have shown limited efficacy.: Objective: The purpose of this study was to investigate whether the aorticorenal ganglion (ARG) can be targeted for renal denervation.: Methods: Twenty-eight ... ...

    Abstract Background: Clinical trials for renal artery (RA) ablation have shown limited efficacy.
    Objective: The purpose of this study was to investigate whether the aorticorenal ganglion (ARG) can be targeted for renal denervation.
    Methods: Twenty-eight pigs were studied under isoflurane or alpha-chloralose to examine hemodynamic responses and catecholamine release in response to RA or ARG stimulation. To assess the efficacy of ARG ablation, we randomized 16 pigs to either sham, RA, or ARG ablation, followed by occlusion of the left anterior descending coronary artery (LAD). Hemodynamic responses, cardiac electrophysiological parameters, and arrhythmias/sudden cardiac death were assessed following LAD occlusion. Absent hemodynamic responses to stimulation confirmed ARG or RA ablation. In vivo stellate ganglion neural activity was recorded to assess cardiac sympathetic signaling. Cadaveric dissections were performed to localize the ARG in humans for comparison to swine.
    Results: The ARG is a purely sympathetic ganglion with cholinergic inputs and pass-through sensory afferent fibers. Compared to RA stimulation, ARG stimulation yielded greater hemodynamic responses during alpha-chloralose anesthesia. However, neither site yielded significant responses under isoflurane. Radiofrequency ablation of the ARG eliminated responses to both RA and ARG stimulation, whereas RA ablation did not eliminate responses to ARG stimulation. Ablation of the ARG did not impact the kidneys or adrenal glands. Compared to control and RA ablation, ARG ablation was protective against ventricular arrhythmias and sudden death. Human and swine ARG are similarly located in the aorticorenal region.
    Conclusion: Our findings indicate that the ARG may be a novel target for renal neuromodulation. Further studies are warranted to validate these findings.
    MeSH term(s) Animals ; Arrhythmias, Cardiac/physiopathology ; Arrhythmias, Cardiac/therapy ; Blood Pressure/physiology ; Disease Models, Animal ; Female ; Heart Rate/physiology ; Kidney/innervation ; Male ; Stellate Ganglion/physiopathology ; Stellate Ganglion/surgery ; Swine ; Sympathectomy/methods
    Language English
    Publishing date 2021-06-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2229357-7
    ISSN 1556-3871 ; 1547-5271
    ISSN (online) 1556-3871
    ISSN 1547-5271
    DOI 10.1016/j.hrthm.2021.06.1192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas.

    Hanna, Peter / Dacey, Michael J / Brennan, Jaclyn / Moss, Alison / Robbins, Shaina / Achanta, Sirisha / Biscola, Natalia P / Swid, Mohammed A / Rajendran, Pradeep S / Mori, Shumpei / Hadaya, Joseph E / Smith, Elizabeth H / Peirce, Stanley G / Chen, Jin / Havton, Leif A / Cheng, Zixi Jack / Vadigepalli, Rajanikanth / Schwaber, James / Lux, Robert L /
    Efimov, Igor / Tompkins, John D / Hoover, Donald B / Ardell, Jeffrey L / Shivkumar, Kalyanam

    Circulation research

    2021  Volume 128, Issue 9, Page(s) 1279–1296

    Abstract: Figure: see text]. ...

    Abstract [Figure: see text].
    MeSH term(s) Adrenergic Neurons/physiology ; Animals ; Atrioventricular Node/innervation ; Atrioventricular Node/physiology ; Autonomic Nervous System/anatomy & histology ; Autonomic Nervous System/physiology ; Biomarkers/analysis ; Cholinergic Neurons/physiology ; Coronary Vessels/anatomy & histology ; Female ; Ganglia, Autonomic/anatomy & histology ; Heart Atria/innervation ; Humans ; Male ; Medical Illustration ; Myocardial Contraction/physiology ; Phenotype ; Sinoatrial Node/innervation ; Sinoatrial Node/physiology ; Swine ; Swine, Miniature ; Synapses/physiology ; Ventricular Function, Left/physiology ; Vesicular Acetylcholine Transport Proteins/analysis
    Chemical Substances Biomarkers ; Slc18a3 protein, mouse ; Vesicular Acetylcholine Transport Proteins
    Language English
    Publishing date 2021-02-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.120.318458
    Database MEDical Literature Analysis and Retrieval System OnLINE

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