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Cited by 88Vagus Nerve Stimulation ResearchHeart Rate Variability and Autonomic ControlCardiac pacing and defibrillation studies

Optogenetic Stimulation of Vagal Efferent Activity Preserves Left Ventricular Function in Experimental Heart Failure

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Machhada, Asif, Hosford, Patrick S., Dyson, Alex, Ackland, Gareth L., Mastitskaya, Svetlana, Gourine, Alexander V.·2020·JACC: Basic to Translational Science
DOI 10.1016/j.jacbts.2020.06.002PMC PMC7452237
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Abstract

Large clinical trials designed to test the efficacy of vagus nerve stimulation (VNS) in patients with heart failure did not demonstrate benefits with respect to the primary endpoints. The nonselective nature of VNS may account for the failure to translate promising results of preclinical and earlier clinical studies. This study showed that optogenetic stimulation of vagal pre-ganglionic neurons transduced to express light-sensitive channels preserved left ventricular function and exercise capacity in a rat model of myocardial infarction-induced heart failure. These data suggested that stimulation of vagal efferent activity is critically important to deliver the therapeutic benefit of VNS in heart failure.

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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 [7]

    The Discussion (page unavailable in our copy) says that cardiac-projecting neurons in the dorsal motor nucleus of the vagus modulate left ventricular contractile properties. It does not establish a cardioinhibitory inotropic effect: stimulation preserved systolic function in rats with heart failure, and the paper says these neurons have relatively little effect on heart rate. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • 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 [7]

    The Results report increased left-ventricular contractility after DVMN stimulation in sham-operated rats, and the Discussion says DVMN cardiac projections modulate ventricular contractile properties. This supports an inotropic effect in healthy animals, but the paper tests optogenetic stimulation rather than establishing that dorsal vagal pathways have a protective role during an unstimulated, normal homeostatic state. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Machhada, A., Hosford, P. S., Dyson, A., Ackland, G. L., Mastitskaya, S., & Gourine, A. V.
Affiliations
  • University College London (GB)
  • Queen Mary University of London (GB)
Corresponding author
  • Mastitskaya, Svetlana
  • Gourine, Alexander V.
ORCID
Venue
JACC: Basic to Translational Science
Publisher
Elsevier BV
Published
2020-08
Volume
5
Issue
8
Pages
799-810
ISSN
2452-302X (ISSN-L)
DOI
10.1016/j.jacbts.2020.06.002
PMC
PMC7452237
OpenAlex
W3042635689
Cited by
88
References
2
Citations by year
2026: 8 · 2025: 16 · 2024: 15 · 2023: 32 · 2022: 6 · 2021: 8 · 2020: 3
FWCI
4.74
Type
journal article
Language
en
Open access
Licence
Locations
  • JACC Basic to Translational Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
Funders
  • University of Bristol
  • Wellcome Trust (095064)
  • Royal College of Anaesthetists
  • H2020 Marie Skłodowska-Curie Actions (654691)
  • Medical Research Council (MR/R01213X/1)
  • Rosetrees Trust
  • British Heart Foundation (RG/14/4/30736, RG/19/5/34463)
Topics
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
Keywords
vagus nerve stimulation, optogenetics, vagal efferent activity, heart failure, left ventricular function, myocardial infarction, exercise capacity, rat model

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