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Cited by 93Cardiac electrophysiology and arrhythmiasHeart Rate Variability and Autonomic ControlVagus Nerve Stimulation Research

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Control of ventricular excitability by neurons of the dorsal motor nucleus of the vagus nerve

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Machhada, Asif, Ang, Richard, Ackland, Gareth L., Ninkina, Natalia, Buchman, Vladimir L., Lythgoe, Mark F., Trapp, Stefan, Tinker, Andrew, Marina, Nephtali, Gourine, Alexander V.·2015·Heart Rhythm
DOI 10.1016/j.hrthm.2015.06.005PMC PMC4631809
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Abstract

BACKGROUND: The central nervous origins of functional parasympathetic innervation of cardiac ventricles remain controversial. OBJECTIVE: This study aimed to identify a population of vagal preganglionic neurons that contribute to the control of ventricular excitability. An animal model of synuclein pathology relevant to Parkinson's disease was used to determine whether age-related loss of the activity of the identified group of neurons is associated with changes in ventricular electrophysiology. METHODS: In vivo cardiac electrophysiology was performed in anesthetized rats in conditions of selective inhibition of the dorsal vagal motor nucleus (DVMN) neurons by pharmacogenetic approach and in mice with global genetic deletion of all family members of the synuclein protein. RESULTS: In rats anesthetized with urethane (in conditions of systemic beta-adrenoceptor blockade), muscarinic and neuronal nitric oxide synthase blockade confirmed the existence of a tonic parasympathetic control of cardiac excitability mediated by the actions of acetylcholine and nitric oxide. Acute DVMN silencing led to shortening of the ventricular effective refractory period (vERP), a lowering of the threshold for triggered ventricular tachycardia, and prolongation of the corrected QT (QTc) interval. Lower resting activity of the DVMN neurons in aging synuclein-deficient mice was found to be associated with vERP shortening and QTc interval prolongation. CONCLUSION: Activity of the DVMN vagal preganglionic neurons is responsible for tonic parasympathetic control of ventricular excitability, likely to be mediated by nitric oxide. These findings provide the first insight into the central nervous substrate that underlies functional parasympathetic innervation of the ventricles and highlight its vulnerability in neurodegenerative diseases.

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  • Recent studies document important influences of cardioinhibitory inotropic vagal fibers originating from the dorsal motor nucleus of the vagus.

    “recent studies document the important influences of cardioinhibitory inotropic vagal fibers originating from the dorsal motor nucleus of the vagus [[5], [6], [7], [8], [9]].”

    From The vagal paradox: A polyvagal solution (2023) · cites this paper as [6]

    The Discussion (page unavailable) reports that dorsal vagal motor nucleus neurons influence ventricular electrical properties, and the Introduction identifies their axons projecting toward cardiac plexuses. The paper studies ventricular excitability and arrhythmia risk, however, not an inotropic effect on cardiac contraction; that part of the description is unsupported. (LLM, conf=0.86)

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  • In a normal homeostatic state, dorsal vagal pathways have a protective ionotropic role on the myocardia.

    “Research suggests that in a normal ‘homeostatic’ state, dorsal vagal pathways have a protective ionotropic role on the myocardia (See Refs. [[5], [6], [7], [8], [9]]).”

    From The vagal paradox: A polyvagal solution (2023) · cites this paper as [6]

    The Discussion (page not supplied) reports that reducing dorsal vagal motor nucleus activity in rat and mouse models produced cardiac electrical changes consistent with a proarrhythmic phenotype, supporting a protective role in ventricular electrical stability. It does not establish an ionotropic mechanism or demonstrate the claim specifically in a normal homeostatic state. (LLM, conf=0.85)

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References 32 · Cited by 93

Research works printed but not linked: 29

  1. Stecker, 2014, Public health burden of sudden cardiac death in the United States, Circ Arrhythm Electrophysiol, 7, 212, 10.1161/CIRCEP.113.001034 · DOI
  2. Olshansky, 2008, Parasympathetic nervous system and heart failure: pathophysiology and potential implications for therapy, Circulation, 118, 863, 10.1161/CIRCULATIONAHA.107.760405 · DOI
  3. La Rovere, 1998, for the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction, Lancet, 351, 478, 10.1016/S0140-6736(97)11144-8 · DOI · Paper page
  4. Hauptman, 2012, Rationale and study design of the increase of vagal tone in heart failure study: INOVATE-HF, Am Heart J, 163, 954, 10.1016/j.ahj.2012.03.021 · DOI
  5. Shen, 2014, Role of the autonomic nervous system in modulating cardiac arrhythmias, Circ Res, 114, 1004, 10.1161/CIRCRESAHA.113.302549 · DOI · Paper page
  6. Ng, 2007, Autonomic modulation of electrical restitution, alternans and ventricular fibrillation initiation in the isolated heart, Cardiovasc Res, 73, 750, 10.1016/j.cardiores.2006.12.001 · DOI
  7. Waxman, 1989, The protective effect of vagus nerve stimulation on catecholamine-halothane-induced ventricular fibrillation in dogs, Can J Physiol Pharmacol, 67, 801, 10.1139/y89-127 · DOI
  8. Waxman, 1988, Modulation of an idioventricular rhythm by vagal tone, J Am Coll Cardiol, 11, 1052, 10.1016/S0735-1097(98)90065-1 · DOI
  9. Schwartz, 1977, Effect of stellectomy and vagotomy on ventricular refractoriness in dogs, Circ Res, 40, 536, 10.1161/01.RES.40.6.536 · DOI
  10. Zuberi, 2010, Absence of the inhibitory G-protein Gαi2 predisposes to ventricular cardiac arrhythmia, Circ Arrhythm Electrophysiol, 3, 391, 10.1161/CIRCEP.109.894329 · DOI
  11. Brack, 2011, Vagus nerve stimulation protects against ventricular fibrillation independent of muscarinic receptor activation, Cardiovasc Res, 91, 437, 10.1093/cvr/cvr105 · DOI
  12. Brack, 2009, Direct evidence of nitric oxide release from neuronal nitric oxide synthase activation in the left ventricle as a result of cervical vagus nerve stimulation, J Physiol, 587, 3045, 10.1113/jphysiol.2009.169417 · DOI
  13. Jones, 1998, Activity of C fibre cardiac vagal efferents in anaesthetized cats and rats, J Physiol, 507, 869, 10.1111/j.1469-7793.1998.869bs.x · DOI
  14. Hopkins, 1997, Anatomy of medullary and peripheral autonomic neurons innervating the neonatal porcine heart, J Auton Nerv Syst, 64, 74, 10.1016/S0165-1838(97)00017-9 · DOI
  15. Mastitskaya, 2012, Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones, Cardiovasc Res, 95, 487, 10.1093/cvr/cvs212 · DOI
  16. Greene, 2014, Causes and consequences of degeneration of the dorsal motor nucleus of the vagus nerve in Parkinson׳s disease, Antioxid Redox Signal, 21, 649, 10.1089/ars.2014.5859 · DOI
  17. Goldberg, 2012, Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson׳s disease, Nat Neurosci, 15, 1414, 10.1038/nn.3209 · DOI
  18. Braak, 2002, Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson׳s disease (preclinical and clinical stages), J Neurol, 249, III/1, 10.1007/s00415-002-1301-4 · DOI
  19. Al-Wandi, 2010, Absence of α-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice, Neurobiol Aging, 31, 796, 10.1016/j.neurobiolaging.2008.11.001 · DOI
  20. Anwar, 2011, Functional alterations to the nigrostriatal system in mice lacking all three members of the synuclein family, J Neurosci, 31, 7264, 10.1523/JNEUROSCI.6194-10.2011 · DOI
  21. Karjalainen, 1994, Relation between QT intervals and heart-rates from 40 to 120 beats/min in rest electrocardiograms of men and a simple method to adjust QT interval values, J Am Coll Cardiol, 23, 1547, 10.1016/0735-1097(94)90654-8 · DOI
  22. Hayes, 1994, Relationship between QaT and RR intervals in rats, guinea-pigs, rabbits, and primates, J Pharmacol Toxicol, 32, 201, 10.1016/1056-8719(94)90088-4 · DOI
  23. Kmecova, 2010, Heart rate correction of the QT duration in rats, Eur J Pharmacol, 641, 187, 10.1016/j.ejphar.2010.05.038 · DOI
  24. Taylor, 1999, Central control of the cardiovascular and respiratory systems and their interactions in vertebrates, Physiol Rev, 79, 855, 10.1152/physrev.1999.79.3.855 · DOI · Paper page
  25. Coronel, 2012, Postrepolarization refractoriness in acute ischemia and after antiarrhythmic drug administration: action potential duration is not always an index of the refractory period, Heart Rhythm, 9, 977, 10.1016/j.hrthm.2012.01.021 · DOI
  26. Zhang, 2014, Measurement and interpretation of electrocardiographic QT intervals in murine hearts, Am J Physiol Heart Circ Physiol, 306, H1553, 10.1152/ajpheart.00459.2013 · DOI
  27. Davis, 2011, Pluripotent stem cell models of cardiac disease and their implication for drug discovery and development, Trends Mol Med, 17, 475, 10.1016/j.molmed.2011.05.001 · DOI
  28. Cerrone, 2005, Bidirectional ventricular tachycardia and fibrillation elicited in a knock-in mouse model carrier of a mutation in the cardiac ryanodine receptor, Circ Res, 96, E77, 10.1161/01.RES.0000169067.51055.72 · DOI
  29. Yutzey, 2007, Principles of genetic murine models for cardiac disease, Circulation, 115, 792, 10.1161/CIRCULATIONAHA.106.682534 · DOI

Metadata

Authors
Machhada, A., Ang, R., Ackland, G. L., Ninkina, N., Buchman, V. L., Lythgoe, M. F., Trapp, S., Tinker, A., Marina, N., & Gourine, A. V.
Affiliations
  • University College London (GB)
  • Queen Mary University of London (GB)
  • Cardiff University (GB)
Corresponding author
Gourine, Alexander V.
ORCID
Venue
Heart Rhythm
Publisher
Elsevier BV
Published
2015-11
Volume
12
Issue
11
Pages
2285-2293
ISSN
1547-5271 (ISSN-L)
DOI
10.1016/j.hrthm.2015.06.005
PMC
PMC4631809
OpenAlex
W1819570725
Cited by
93
References
32
Citations by year
2026: 4 · 2025: 7 · 2024: 9 · 2023: 11 · 2022: 3 · 2021: 13 · 2020: 9 · 2019: 3 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 4
FWCI
8.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Heart Rhythm (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, other-oa)
Funders
  • Wellcome Trust (075615)
  • National Institute for Health and Care Research
  • British Heart Foundation (FS/13/5/29927, RG/14/4/30736)
  • Diabetes UK (12/0004529)
  • Rosetrees Trust (M156-F1)
  • Medical Research Council
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Keywords
vagal preganglionic neurons, ventricular excitability, ventricular effective refractory period, QTc interval, ventricular tachycardia, synuclein, Parkinson's disease, neurodegeneration, nitric oxide, acetylcholine, cardiac electrophysiology, aging
MeSH terms
Animals, Disease Models, Animal, Heart Ventricles, Male, Mice, Inbred C57BL, Random Allocation, Vagus Nerve, Rats, Sprague-Dawley, Parasympathectomy, Statistics, Nonparametric, Mice, Rats, Nitric Oxide Synthase Type I, Cardiac Electrophysiology, Vagus Nerve Stimulation

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