Electrophysiological effects of ivabradine in dog and human cardiac preparations: Potential antiarrhythmic actions

István Koncz, Tamás Szél, Miklós Bitay, Elisabetta Cerbai, Kristian Jaeger, Ferenc Fülöp, Norbert Jost, László Virág, Péter Orvos, László Tálosi, Attila Kristóf, István Baczkó, Julius Gy Papp, András Varró

Research output: Article

32 Citations (Scopus)

Abstract

Ivabradine is a novel antianginal agent which inhibits the pacemaker current. The effects of ivabradine on maximum rate of depolarization (V max), repolarization and spontaneous depolarization have not yet been reported in human isolated cardiac preparations. The same applies to large animals close to human in heart size and spontaneous frequency. Using microelectrode technique action potential characteristics and by applying patch-clamp technique ionic currents were studied. Ivabradine exerted concentration-dependent (0.1-10 μM) decrease in the amplitude of spontaneous diastolic depolarization and reduction in spontaneous rate of firing of action potentials and produced a concentration- and frequency-dependent V max block in dog Purkinje fibers while action potential duration measured at 50% of repolarization was shortened. In the presence of ivabradine, at 400 ms cycle length, V max block developed with an onset kinetic rate constant of 13.9 ± 3.2 beat -1 in dog ventricular muscle. In addition to a fast recovery of V max from inactivation (τ = 41-46 ms) observed in control, a second slow component for recovery of V max was expressed (offset kinetics of V max block) having a time constant of 8.76 ± 1.34 s. In dog after attenuation of the repolarization reserve ivabradine moderately but significantly lengthened the repolarization. In human, significant prolongation of repolarization was only observed at 10 μM ivabradine. Ivabradine in addition to the Class V antiarrhythmic effect also has Class I/C and Class III antiarrhythmic properties, which can be advantageous in the treatment of patients with ischemic heart disease liable to disturbances of cardiac rhythm.

Original languageEnglish
Pages (from-to)419-426
Number of pages8
JournalEuropean Journal of Pharmacology
Volume668
Issue number3
DOIs
Publication statusPublished - okt. 15 2011

ASJC Scopus subject areas

  • Pharmacology

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