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

Abstract

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.

Reduced N‐Type Ca 2+ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

“…Based on the fact that the occurrence of fatal ventricular arrhythmias is accompanied by a marked decrease of parasympathetic activity in CHF, some studies demonstrate that decreased parasympathetic activity is correlated with malignant ventricular arrhythmogenesis in the CHF state 11, 46, 47, 48. Recent studies have also found that the parasympathetic activation induced by vagal nerve stimulation prevents fatal ventricular arrhythmias and improves survival rates in animal CHF models 17, 18, 19. However, there is no direct evidence to clarify the role of decreased parasympathetic activity in ventricular arrhythmogenesis and how decreased parasympathetic activity links to ventricular arrhythmogenesis in CHF due to the coexistence of multiple factors in the CHF state (such as sympathetic overactivation, ventricular morphological changes, and others).…”

“…However, such pharmacological treatment is not ideal because the ability of β‐adrenergic receptor blockers to affect cardiac vagal activity is limited,15 and survival rates even when β‐blockers are used are lower in CHF patients with depressed cardiac vagal activity than in CHF patients with normal cardiac vagal activity 16. Although modulation of cardiac vagal activation as a potential therapy has received only limited attention, direct cardiac vagal nerve stimulation has been found to suppress ventricular tachyarrhythmia and to improve survival rates in CHF 17, 18, 19. Therefore, exploring the mechanism(s) responsible for the impairment of cardiac vagal function can provide a new therapeutic strategy for eliminating ventricular tachyarrhythmia and reducing related mortality.…”

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control

“…Given the critical role of the vagus nerve in providing parasympathetic innervation to the heart, there has been interest in using VNS to modulate cardiac function. In animals, electrical stimulation of the cervical vagus nerve has been shown to evoke cardiovascular effects, for example by lowering the ventricular fibrillation threshold (Brack et al, 2013). Moreover, VNS is known to reduce incidence of ventricular arrhythmias and mortality during ischemia (Brack et al, 2013) and prevent sudden cardiac death in dogs with myocardial infarction (Vanoli et al, 1991).…”

“…In animals, electrical stimulation of the cervical vagus nerve has been shown to evoke cardiovascular effects, for example by lowering the ventricular fibrillation threshold (Brack et al, 2013). Moreover, VNS is known to reduce incidence of ventricular arrhythmias and mortality during ischemia (Brack et al, 2013) and prevent sudden cardiac death in dogs with myocardial infarction (Vanoli et al, 1991). VNS has also been investigated in animal models of chronic heart failure, a condition characterised by a sustained increase in sympathetic drive and a concurrent withdrawal of parasympathetic activity (Triposkiadis et al, 2009).…”

Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis

“…15 Autonomic regulation of the heart plays a key role in cardiovascular functioning. 16,17 Poor cardiac autonomic regulation has been implicated in heart failure, 18,19 and increased vagal input (through vagal nerve stimulation or pharmacological modulators) is protective against ventricular fibrillation 20,21 and sudden cardiac death. 22 Heart rate variability (HRV), the assessment of beat-to-beat variation in the heart over time, provides a reliable index of cardiac autonomic funtion.…”