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 (1), p. 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/ | ||||||||||||||||||||||||||||||||||||||||||||
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Document Type: | Article | ||||||||||||||||||||||||||||||||||||||||||||
Title: | Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation | ||||||||||||||||||||||||||||||||||||||||||||
Authors: |
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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 | ||||||||||||||||||||||||||||||||||||||||||||
Page Range: | p. 7748 | ||||||||||||||||||||||||||||||||||||||||||||
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 - Research under Space Conditions | ||||||||||||||||||||||||||||||||||||||||||||
DLR - Research theme (Project): | R - Vorhaben Systemphysiologie (old) | ||||||||||||||||||||||||||||||||||||||||||||
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: | 08 Nov 2023 14:35 |
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