Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

Abstract

The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesis.

Epicardial ganglionated plexi ablation increases the inducibility of ventricular tachyarrhythmias in a canine postmyocardial infarction model

“…Several lines of clinical evidence show that the addition of GP ablation to pulmonary vein isolation confers a significantly higher success rate compared with pulmonary vein isolation only in patients with atrial fibrillation . However, GP ablation, which destroys the intrinsic cardiac autonomic nervous system, may potentially have impacts on ventricular electrophysiology and arrhythmogenesis . Previous studies by He et al showed that GP stimulation significantly decreased the incidence of ventricular arrhythmias (VA) in a canine model of acute myocardial ischemia, whereas GP ablation had the opposite effect .…”

“…4,5 However, GP ablation, which destroys the intrinsic cardiac autonomic nervous system, may potentially have impacts on ventricular electrophysiology and arrhythmogenesis. 6 Previous studies by He et al 7,8 showed that GP stimulation significantly decreased the incidence of ventricular arrhythmias (VA) in a canine model of acute myocardial ischemia, whereas GP ablation had the opposite effect. 9 However, the long-term effect of GP ablation on ventricular electrophysiology in a canine postmyocardial infarction (MI) model is still unknown.…”

Over-expression of arginine vasopressin in magnocellular neurosecretory cells of hypothalamus and its potential relationship with development of diabetic nephropathy

“…Furthermore, our results above suggested that the neurodegeneration and apoptosis may be due to the upregulation of AVP. In addition, a recent study reported that disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias [33]. Accordingly, we speculated that AVP may exert a destructive role in heart neurons.…”

Precursor proadrenomedullin influences cardiomyocyte survival and local inflammation related to myocardial infarction

“…For histological studies, cross-sections of murine hearts were stained using H&E staining. Furthermore, specific proteins were detected by immunofluorescent staining of cross-sections or cardiac cells as described previously (64). Staining was carried out according to the detailed protocol described in SI Appendix.…”