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Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation

Chobanyan-Jürgens, C. and Heusser, K. and Duncker, D. and Veltmann, C. and May, M. and Mehling, H. and Luft, F.C. and Schröder, C. and Jordan, J. and Tank, J. (2018) Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation. Scientific Reports, 8 (7748). Nature Publishing Group. DOI: 10.1038/s41598-018-26099-9 ISSN 2045-2322

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Official URL: http://www.nature.com/scientificreports/

Abstract

Clinical trials and studies with ivabradine implicate cardiac pacemaker channels (HCN4) in the pathogenesis of atrial arrhythmias. Because acute changes in cardiac autonomic tone predispose to atrial arrhythmias, we studied humans in whom profound cardiac sympathetic activation was rapidly relieved to test infuences of HCN4 inhibition with ivabradine on atrial arrhythmias. We tested 19 healthy participants with ivabradine, metoprolol, or placebo in a double blind, randomized, cross-over fashion on top of selective norepinephrine reuptake inhibition with reboxetine. Subjects underwent combined head up tilt plus lower body negative pressure testing followed by rapid return to the supine position. In the current secondary analysis with predefned endpoints before data unblinding, continuous fnger blood pressure and ECG recordings were analyzed by two experienced cardiac electrophysiologists and a physician, blinded for treatment assignment. The total atrial premature activity (referred to as atrial events) at baseline did not difer between treatments. After backwards tilting, atrial events were signifcantly higher with ivabradine compared with metoprolol or with placebo. Unlike beta-adrenoreceptor blockade, HCN4 inhibition while lowering heart rate does not protect from atrial arrhythmias under conditions of experimental cardiac sympathetic activation. The model in addition to providing insight in the role of HCN4 in human atrial arrhythmogenesis may have utility in gauging potential atrial pro-arrhythmic drug properties.

Item URL in elib:https://elib.dlr.de/125065/
Document Type:Article
Title:Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Chobanyan-Jürgens, C.UNSPECIFIEDUNSPECIFIED
Heusser, K.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIED
Duncker, D.Department of Cardiology and Angiology, Hannover Medical School, GermanyUNSPECIFIED
Veltmann, C.Department of Cardiology and Angiology, Hannover Medical School, GermanyUNSPECIFIED
May, M.Institute for Clinical Pharmacology, MHH, GermanyUNSPECIFIED
Mehling, H.Experimental Clinical Research Center, Charité Medical Faculty and Max Delbrück Center for Molecular Medicine, BerlinUNSPECIFIED
Luft, F.C.franz-volhard clinical research center, medical university charité, campus buch, berlin, germanyUNSPECIFIED
Schröder, C.Institute of Clinical Pharmacology, Hannover Medical School, GermanyUNSPECIFIED
Jordan, J.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIED
Tank, J.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIED
Date:17 May 2018
Journal or Publication Title:Scientific Reports
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:8
DOI :10.1038/s41598-018-26099-9
Publisher:Nature Publishing Group
Series Name:Scientific Reports
ISSN:2045-2322
Status:Published
Keywords:Clinical trials and studies; sympathetic and parasympathetic nervous System; tested
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Systemphysiologie
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Cardiovascular Medicine in Aerospace
Deposited By: Schrage, Larissa
Deposited On:18 Dec 2018 10:33
Last Modified:18 Dec 2018 10:33

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