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

Scientific Reports
Kristine Chobanyan-JürgensJens Tank

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 influences 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 predefined endpoints before data unblinding, continuous finger 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 differ between treatments. After backwards tilting, atrial events were significantly higher with ivabradine compared with metoprolol or with placebo. Unlike beta-adrenoreceptor blockade, HCN4 inhibition whi...Continue Reading

References

Feb 14, 1991·The New England Journal of Medicine·J LeitchW S Teo
Jul 1, 1985·The Journal of Clinical Investigation·D S GoldsteinI J Kopin
May 1, 1983·Pacing and Clinical Electrophysiology : PACE·P CoumelJ F Leclercq
Oct 1, 1996·Journal of Cardiovascular Electrophysiology·P Coumel
Feb 24, 2000·The New England Journal of Medicine·J R ShannonD Robertson
Jun 27, 2002·The Journal of General Physiology·Annalisa BucchiDario DiFrancesco
Jul 12, 2005·Current Medical Research and Opinion·Dario DiFrancesco
Jan 13, 2006·The New England Journal of Medicine·Raffaella MilanesiDario DiFrancesco
Jun 21, 2006·Journal of Psychopharmacology·Murray EslerGavin Lambert
Jul 19, 2006·Basic Research in Cardiology·Masamichi Hirose, Hiroshi Imamura
Jan 13, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Victor A Maltsev, Edward G Lakatta
Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Mirko BaruscottiDario DiFrancesco
Sep 20, 2011·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Victor A Maltsev, Edward G Lakatta
Jun 23, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Richard BaylesAssam El-Osta
Mar 13, 2014·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Vincenzo MacriPatrick T Ellinor
Apr 20, 2014·Frontiers in Pharmacology·Yael Yaniv, Victor A Maltsev
Sep 21, 2015·International Journal of Cardiology·Caminiti GiuseppeVolterrani Maurizio
Mar 24, 2016·Journal of Cardiovascular Electrophysiology·Zainab Abdel-Salam, Wail Nammas

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Citations

Sep 8, 2018·The Journal of Physiological Sciences : JPS·Toru KawadaMasaru Sugimachi
Aug 11, 2019·Current Topics in Medicinal Chemistry·Yue ZhouKun Sun
Mar 20, 2021·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Mariusz MarciszekMichał Mączewski

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Methods Mentioned

BETA
coronary artery bypass

Clinical Trials Mentioned

NCT00865917

Software Mentioned

GraphPad
GraphPad Prism
Windaq pro +

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