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

Asif Machhada1, Patrick S Hosford1,2, Alex Dyson3

  • 1Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.

JACC. Basic to Translational Science
|September 3, 2020
PubMed

Insights

Optogenetic stimulation of vagal nerves improved heart function in rats with heart failure. Targeting vagal efferent activity is key for vagus nerve stimulation (VNS) therapy in heart failure patients.

Area of Science:

  • Cardiology
  • Neuroscience
  • Biomedical Engineering

Background:

  • Vagus nerve stimulation (VNS) trials for heart failure yielded inconclusive results.
  • Nonselective VNS may explain the lack of efficacy in clinical settings.
  • Preclinical studies suggested VNS benefits for heart failure.

Purpose of the Study:

  • To investigate the therapeutic potential of targeted vagal efferent nerve stimulation.
  • To determine if optogenetic stimulation of specific vagal neurons can improve cardiac function in heart failure models.

Main Methods:

  • Utilized optogenetics to stimulate vagal pre-ganglionic neurons in a rat model of myocardial infarction-induced heart failure.
  • Engineered neurons to express light-sensitive channels for precise stimulation.
  • Assessed left ventricular function and exercise capacity post-stimulation.

Main Results:

  • Optogenetic stimulation preserved left ventricular function.
  • Exercise capacity was maintained in the treated heart failure rat model.
  • Demonstrated the efficacy of targeted vagal efferent stimulation.

Conclusions:

  • Targeted stimulation of vagal efferent pathways is crucial for VNS therapeutic benefits in heart failure.
  • Optogenetics offers a precise method to modulate vagal activity for cardiac therapy.
  • Future research should focus on selective VNS strategies for heart failure.
Keywords:
ABP, arterial blood pressureDVMN, dorsal motor nucleus of the vagus nerveGRK2, G-protein−coupled receptor kinase 2LAD, left anterior descending coronary arteryLV dP/dtMAX, maximum rate of rise of left ventricular pressureLV, left ventricleLVEDP, left ventricular end-diastolic pressureLVESP, left ventricular end-systolic pressureLVP, left ventricular pressureLVV, lentiviral vectorMI, myocardial infarctionVNS, vagus nerve stimulationautonomic nervous systemeGFP, enhanced green fluorescent proteinheart failuremyocardial infarctionneuromodulationvagus nerve stimulation

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