کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2532495 1559015 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Electrophysiological effects of ivabradine in dog and human cardiac preparations: Potential antiarrhythmic actions
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Electrophysiological effects of ivabradine in dog and human cardiac preparations: Potential antiarrhythmic actions
چکیده انگلیسی

Ivabradine is a novel antianginal agent which inhibits the pacemaker current. The effects of ivabradine on maximum rate of depolarization (Vmax), 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 Vmax 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, Vmax 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 Vmax from inactivation (τ = 41–46 ms) observed in control, a second slow component for recovery of Vmax was expressed (offset kinetics of Vmax 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 668, Issue 3, 15 October 2011, Pages 419–426
نویسندگان
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