Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

Christiane Jungen, Katharina Scherschel, Christian Eickholt, Pawel Kuklik, Niklas Klatt, Nadja Bork, Tim Salzbrunn, Fares Alken, Stephan Angendohr, Christiane Klene, Janos Mester, Nikolaj Klöcker, Marieke W. Veldkamp, Udo Schumacher, Stephan Willems, Viacheslav O. Nikolaev () and Christian Meyer ()
Additional contact information
Christiane Jungen: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf
Katharina Scherschel: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf
Christian Eickholt: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf
Pawel Kuklik: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf
Niklas Klatt: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf
Nadja Bork: DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck
Tim Salzbrunn: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf
Fares Alken: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf
Stephan Angendohr: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf
Christiane Klene: University Medical Center Hamburg-Eppendorf
Janos Mester: University Medical Center Hamburg-Eppendorf
Nikolaj Klöcker: Institute of Neural and Sensory Physiology, Medical Faculty, University of Düsseldorf
Marieke W. Veldkamp: Academic Medical Center, University of Amsterdam
Udo Schumacher: Institute of Anatomy and Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf
Stephan Willems: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf
Viacheslav O. Nikolaev: DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck
Christian Meyer: cardiac Neuro- and Electrophysiology Research Group (cNEP), University Heart Center, University Hospital Hamburg-Eppendorf

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14155

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