The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation

Author： Wettwer Erich Christ Torsten Endig Sebastian Rozmaritsa Nadiia Matschke Klaus Lynch Joseph J. Pourrier Marc Gibson John K. Fedida David Knaut Michael Ravens Ursula

Publisher： Oxford University Press

ISSN： 0008-6363

Source： Cardiovascular Research, Vol.98, Iss.1, 2013-04, pp. : 145-154

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

AimsVernakalant is a newly developed antiarrhythmic drug against atrial fibrillation (AF). However, its electrophysiological actions on human myocardium are unknown.Methods and resultsAction potentials (APs) and ion currents were recorded in right atrial trabeculae and cardiomyocytes from patients in sinus rhythm (SR) and chronic AF. Vernakalant prolonged early repolarization in SR and AF, but late only in AF. AP amplitude (APA) and dV/dt_max were reduced in a concentration- and frequency-dependent manner with IC₅₀ < 10 µM at >3 Hz. Effective refractory period was increased more than action potential duration (APD) in SR and AF. I_Na was blocked with IC₅₀s of 95 and 84 µM for SR and AF, respectively (0.5 Hz). Vernakalant did not reduce outward potassium currents compared with time-matched controls. However, area under the current-time curve was reduced due to acceleration of current decline with IC₅₀s of 19 and 12 µM for SR and AF, respectively. Vernakalant had less effect on APD than the I_Kr blocker E-4031, blocked I_K,ACh, and had a small inhibitory effect on I_K1 at 30 µM. L-Type Ca²⁺ currents (SR) were reduced with IC₅₀ of 84 µM.ConclusionRate-dependent block of Na⁺ channels represents the main antiarrhythmic mechanism of vernakalant in the fibrillating atrium. Open channel block of early transient outward currents and I_K,ACh could also contribute.