Mechanisms underlying the autonomic modulation of ventricular fibrillation initiation--tentative prophylactic properties of vagus nerve stimulation on malignant arrhythmias in heart failure

Heart Fail Rev. 2013 Jul;18(4):389-408. doi: 10.1007/s10741-012-9314-2.


Classical physiology teaches that vagal post-ganglionic nerves modulate the heart via acetylcholine acting at muscarinic receptors, whilst it is accepted that vagus nerve stimulation (VNS) slows heart rate, atrioventricular conduction and decreases atrial contraction; there is continued controversy as to whether the vagus has any significant direct effect on ventricular performance. Despite this, there is a significant body of evidence from experimental and clinical studies, demonstrating that the vagus nerve has an anti-arrhythmic action, protecting against induced and spontaneously occurring ventricular arrhythmias. Over 100 years ago Einbrodt first demonstrated that direct cervical VNS significantly increased the threshold for experimentally induced ventricular fibrillation. A large body of evidence has subsequently been collected supporting the existence of an anti-arrhythmic effect of the vagus on the ventricle. The development of prognostic indicators of heart rate variability and baroreceptor reflex sensitivity--measures of parasympathetic tone and reflex activation respectively--and the more recent interest in chronic VNS therapy are a direct consequence of the earlier experimental studies. Despite this, mechanisms underlying the anti-arrhythmic actions of the vagus nerve have not been fully characterised and are not well understood. This review summarises historical and recently published data to highlight the importance of this powerful endogenous protective phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Endothelium-Dependent Relaxing Factors / metabolism
  • Evidence-Based Medicine
  • Heart Conduction System / physiopathology*
  • Heart Failure / complications
  • Heart Failure / metabolism
  • Heart Failure / physiopathology*
  • Heart Failure / therapy*
  • Humans
  • Nitric Oxide / metabolism
  • Prognosis
  • Receptors, Muscarinic / metabolism
  • Vagus Nerve / physiopathology*
  • Vagus Nerve Stimulation*
  • Vasodilator Agents / metabolism
  • Ventricular Fibrillation / etiology
  • Ventricular Fibrillation / metabolism
  • Ventricular Fibrillation / physiopathology*
  • Ventricular Fibrillation / prevention & control*


  • Endothelium-Dependent Relaxing Factors
  • Receptors, Muscarinic
  • Vasodilator Agents
  • Nitric Oxide
  • Acetylcholine