Ivabradine Aggravates the Proarrhythmic Risk in Experimental Models of Long QT Syndrome

Cardiovascular Toxicology
Gerrit FrommeyerLars Eckardt

Abstract

Ivabradine has recently been demonstrated to have antiarrhythmic properties in atrial fibrillation. The aim of the present study was to assess the electrophysiologic profile of ivabradine in an experimental whole-heart model of long-QT-syndrome. In 12 isolated rabbit hearts long-QT-2-syndrome (LQT2) was simulated by infusion of D,L-sotalol (100 µM). 12 rabbit hearts were treated with veratridine (0.5 µM) to mimic long-QT-3-syndrome (LQT3). Sotalol induced a significant prolongation of QT-interval (+ 40 ms, p < 0.01) and action potential duration (APD, + 20 ms, p < 0.01). Similar results were obtained in veratridine-treated hearts (QT-interval: +52 ms, p < 0.01; APD: + 41 ms, p < 0.01). Of note, both sotalol (+ 26 ms, p < 0.01) and veratridine (+ 42 ms, p < 0.01) significantly increased spatial dispersion of repolarisation. Additional infusion of ivabradine (5 µM) did not change these parameters in sotalol-pretreated hearts but resulted in a further significant increase of QT-interval (+ 26 ms, p < 0.05) and APD (+ 49 ms, p < 0.05) in veratridine-treated hearts. Lowering of potassium concentration in bradycardic AV-blocked hearts resulted in the occurrence of early afterdepolarizations (EAD) or polymorphic ventricular tachycardi...Continue Reading

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Nov 20, 2016·International Journal of Cardiology·Gerrit FrommeyerLars Eckardt
Mar 7, 2017·International Journal of Cardiology·Gerrit FrommeyerLars Eckardt
Apr 30, 2017·BMC Cardiovascular Disorders·Hayelom Gebrekirstos MengeshaAbraha Hailu
May 31, 2017·Clinical and Experimental Pharmacology & Physiology·Gerrit FrommeyerLars Eckardt
Jun 15, 2017·Cardiovascular Toxicology·Gerrit FrommeyerLars Eckardt
Jun 20, 2017·Basic & Clinical Pharmacology & Toxicology·Gerrit FrommeyerLars Eckardt
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Citations

Nov 15, 2018·Journal of Cardiovascular Electrophysiology·Sara N Koenig, Peter J Mohler
Aug 11, 2019·Current Topics in Medicinal Chemistry·Yue ZhouKun Sun
Nov 2, 2021·Biological & Pharmaceutical Bulletin·Akira TakaharaYoshinobu Nagasawa

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Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology
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