title: The new antiarrhythmic drug vernakalant: ex vivo study of human atrial tissue from sinus rhythm and chronic atrial fibrillation.
abstract: OBJECTIVE
  Vernakalant is a newly developed antiarrhythmic drug against atrial fibrillation (AF). However, its electrophysiological actions on human myocardium are unknown.
  
  
  RESULTS
  Action 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/dtmax 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. INa 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 IKr blocker E-4031, blocked IK,ACh, and had a small inhibitory effect on IK1 at 30 µM. L-Type Ca(2+) currents (SR) were reduced with IC50 of 84 µM.
  
  
  CONCLUSIONS
  Rate-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 IK,ACh could also contribute.
authors: Department of Pharmacology and Toxicology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Fetscherstraße 74, Dresden D-01307, Germany. ravens@rcs.urz.tu-dresden.de
authors: Erich
authors: E
authors: Wettwer
authors: Torsten
authors: T
authors: Christ
authors: Sebastian
authors: S
authors: Endig
authors: Nadiia
authors: N
authors: Rozmaritsa
authors: Klaus
authors: K
authors: Matschke
authors: Joseph J
authors: JJ
authors: Lynch
authors: Marc
authors: M
authors: Pourrier
authors: John K
authors: JK
authors: Gibson
authors: David
authors: D
authors: Fedida
authors: Michael
authors: M
authors: Knaut
authors: Ursula
authors: U
authors: Ravens
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000368:Aged; D000840:Anisoles / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001146:Arrhythmia, Sinus / Q000188:drug therapy*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D015220:Calcium Channels / Q000187:drug effects; D002908:Chronic Disease; D005260:Female; D006325:Heart Atria / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects
chemical_list: D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D015221:Potassium Channels; D011759:Pyrrolidines; D015222:Sodium Channels; C524581:vernakalant