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.
Highlights
The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation
ventricular refractory periods (VRPs) were shorter in partial atrial denervation (PAD) hearts (23.4±0.9 ms) compared with control hearts (31.6±2.2 ms, P 1⁄4 0.003, unpaired t-test; Fig. 1d), similar to atrial refractory periods, demonstrating that disruption of cardiac neurons distant from the ventricles influences ventricular baseline electrophysiology
The major findings of the present study are as follows: (i) morphological and functional evidence support that cardiac cholinergic neurons regulate ventricular electrophysiology; (ii) modulation of the atrial neural network changes left ventricular Cyclic adenosine monophosphate (cAMP) levels; (iii) accidental partial atrial denervation during catheter ablation of atrial fibrillation (AF) is characterized by both reduced parasympathetic activity and disturbed sympathetic ventricular control
Summary
The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. 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. Cardiac neurons are inevitably obliterated during catheter ablation[4], which is the therapy of choice for most patients suffering from symptomatic AF This technique is a minimally invasive procedure performed to deactivate specific areas of abnormal firing heart tissue especially in the left atrium around the pulmonary veins. Experimental data confirm that mechanical disruption or pharmacological blockade of cardiac parasympathetic innervation shortens ventricular refractory periods (VRPs), increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in mouse hearts. The results imply a vital role of atrial cholinergic neurons in the modulation of ventricular electrophysiology
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