Author + information
- Received December 9, 2019
- Revision received June 5, 2020
- Accepted June 6, 2020
- Published online August 24, 2020.
- Asif Machhada, PhDa,
- Patrick S. Hosford, PhDa,b,
- Alex Dyson, PhDc,
- Gareth L. Ackland, PhDb,
- Svetlana Mastitskaya, PhDa,∗∗ ( and )
- Alexander V. Gourine, PhDa,∗ ()
- aCentre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
- bTranslational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
- cClinical Physiology, Division of Medicine, University College London, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Alexander V. Gourine, Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
- ↵∗∗Dr. Svetlana Mastitskaya, Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
• This study was designed to determine the effect of selective optogenetic simulation of vagal efferent activity on left ventricular function in an animal (rat) model of MI-induced heart failure.
• Optogenetic stimulation of dorsal brainstem vagal pre-ganglionic neurons transduced to express light-sensitive channels preserved LV function and exercise capacity in animals with MI.
• The data suggest that activation of vagal efferents is critically important to deliver the therapeutic benefit of VNS in chronic heart failure.
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.
This work was supported by the British Heart Foundation (Ref: RG/14/4/30736 and RG/19/5/34463) and Medical Research Council (Ref: MR/R01213X/1). Dr. Gourine was supported by the Wellcome Trust Senior Research Fellowship (Ref: 095064). Dr. Mastitskaya was supported by Marie Skłodowska-Curie Research Fellowship (Ref: 654691). Dr. Machhada was supported by the Medical Research Council and The Rosetrees Trust. Dr. Ackland was supported by British Journal of Anaesthesia/Royal College of Anaesthetists Basic Science Career Development Award and the BOC research chair grant in anaesthesia from the Royal College of Anaesthetists. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received December 9, 2019.
- Revision received June 5, 2020.
- Accepted June 6, 2020.
- 2020 The Authors