title: Antiarrhythmic effect of vernakalant in an experimental model of Long-QT-syndrome.
abstract: OBJECTIVE
  The antiarrhythmic drug vernakalant exerts antiarrhythmic effects in atrial fibrillation. Recent experimental data suggest interactions with the late sodium current and antiarrhythmic effects in ventricular arrhythmias. We aimed at investigating whether treatment with vernakalant reduces polymorphic ventricular tachycardia (VT) in an experimental model of Long-QT-syndrome (LQTS).
  
  
  RESULTS
  Twenty-nine isolated rabbit hearts were assigned to two groups and treated with erythromycin (300 µM, n = 15) or veratridine (0.5 µM, n = 14) after obtaining baseline data. Thereafter, vernakalant (10 µM) was additionally infused. Infusion of erythromycin or veratridine significantly increased action potential duration (APD90) and QT interval. Erythromycin and veratridine also significantly augmented spatial dispersion of repolarization (erythromycin: +43 ms; veratridine: +55 ms, P < 0.01, respectively) and temporal dispersion of repolarization. After lowering extracellular [K+] in bradycardic hearts, 11 of 15 erythromycin-treated hearts and 4 of 14 veratridine-treated hearts showed early afterdepolarizations and subsequent polymorphic VT. Additional treatment with vernakalant resulted in a significant reduction of spatial dispersion of spatial dispersion in both groups (erythromycin: -32 ms; veratridine: -35 ms, P < 0.05 each) and a stabilization of temporal dispersion. After additional treatment with vernakalant, only 5 of 15 erythromycin-treated hearts (P = 0.07) and 1 of 14 veratridine-treated hearts (P = 0.32) presented polymorphic VT.
  
  
  CONCLUSIONS
  Vernakalant has antiarrhythmic effects in this experimental model of acquired LQTS. A reduction of spatial dispersion of repolarization and a stabilization of temporal dispersion in hearts showing polymorphic VT represent the major underlying electrophysiological mechanisms.
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Albert-Schweitzer Campus 1, D-48149 Münster, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Frommeyer
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Albert-Schweitzer Campus 1, D-48149 Münster, Germany.
authors.forename: Catharina
authors.initials: C
authors.lastname: Clauss
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Albert-Schweitzer Campus 1, D-48149 Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ellermann
authors.affiliation: Märkische Kliniken GmbH, Department of Cardiology and Angiology, Klinikum Lüdenscheid, University of Witten-Herdecke, Witten, Germany.
authors.forename: Harilaos
authors.initials: H
authors.lastname: Bogossian
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Albert-Schweitzer Campus 1, D-48149 Münster, Germany.
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Dechering
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Albert-Schweitzer Campus 1, D-48149 Münster, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Kochhäuser
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Albert-Schweitzer Campus 1, D-48149 Münster, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Reinke
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Albert-Schweitzer Campus 1, D-48149 Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pott
authors.affiliation: Division of Clinical and Experimental Electrophysiology, Department of Cardiology and Angiology, University Hospital of Münster, Albert-Schweitzer Campus 1, D-48149 Münster, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
mesh_terms: D000818:Animals; D000840:Anisoles / Q000008:administration & dosage*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D008133:Long QT Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D011759:Pyrrolidines / Q000008:administration & dosage*; D011817:Rabbits; D017180:Tachycardia, Ventricular / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; C524581:vernakalant
keywords: Dispersion of repolarization; Pro-arrhythmia; Repolarization reserve; Vernakalant-acquired long-QT-syndrome