Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias
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Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias. / Jungen, Christiane; Scherschel, Katharina; Eickholt, Christian; Kuklik, Pawel; Klatt, Niklas; Bork, Nadja; Salzbrunn, Tim; Alken, Fares; Angendohr, Stephan; Klene, Christiane; Mester, Janos; Klöcker, Nikolaj; Veldkamp, Marieke W; Schumacher, Udo; Willems, Stephan; Nikolaev, Viacheslav O; Meyer, Christian.
in: NAT COMMUN, Jahrgang 8, 14155, 27.01.2017.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias
AU - Jungen, Christiane
AU - Scherschel, Katharina
AU - Eickholt, Christian
AU - Kuklik, Pawel
AU - Klatt, Niklas
AU - Bork, Nadja
AU - Salzbrunn, Tim
AU - Alken, Fares
AU - Angendohr, Stephan
AU - Klene, Christiane
AU - Mester, Janos
AU - Klöcker, Nikolaj
AU - Veldkamp, Marieke W
AU - Schumacher, Udo
AU - Willems, Stephan
AU - Nikolaev, Viacheslav O
AU - Meyer, Christian
PY - 2017/1/27
Y1 - 2017/1/27
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/ncomms14155
DO - 10.1038/ncomms14155
M3 - SCORING: Journal article
C2 - 28128201
VL - 8
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
M1 - 14155
ER -