title: Interactions of digitalis and class-III antiarrhythmic drugs: Amiodarone versus dronedarone.
abstract: BACKGROUND
  A post hoc analysis of the PALLAS trial suggested possible interactions of dronedarone and digitalis glycosides. The aim of the present study was to compare the effects dronedarone or amiodarone in combination with digitalis glycosides.
  
  
  RESULTS
  Eleven female rabbits underwent chronic oral treatment with amiodarone (50mg/kg/d for 6weeks). Ten rabbits were treated with dronedarone (50mg/kg/d for 6weeks). Ten rabbits were used as controls. Hearts were isolated and Langendorff-perfused. Monophasic action potentials and ECG showed a moderate prolongation of QT interval and action potential duration (APD). Both drugs also increased effective refractory period. Additional application of ouabain (0.2μM) resulted in a significant decrease of QT interval, APD, and ERP in all groups. Ventricular arrhythmias were induced by programmed ventricular stimulation and aggressive burst stimulation. Reproducible occurrence was defined as occurrence of at least 3 episodes. Under baseline conditions in control hearts, ventricular fibrillation (VF) was inducible in 1 of 10 hearts (7 episodes). After the application of 0.2μM ouabain, 4 of 10 control hearts were inducible (24 episodes). One of 10 dronedarone-pretreated hearts (3 episodes) and 2 of 11 amiodarone-pretreated hearts (6 episodes) showed VF before ouabain infusion. After the application of 0.2μM ouabain, 7 of 10 dronedarone-pretreated hearts were inducible (73 episodes). By contrast, only 4 of 11 amiodarone-pretreated hearts (13 episodes) showed VF.
  
  
  CONCLUSIONS
  In the present study, additional treatment with ouabain resulted in an increased ventricular vulnerability in al study groups. Of note, chronically dronedarone-pretreated hearts were significantly more vulnerable than amiodarone-pretreated hearts.
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany. Electronic address: gerrit.frommeyer@ukmuenster.de.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Frommeyer
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Puckhaber
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ellermann
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Dechering
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Kochhäuser
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Leitz
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Reinke
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004195:Disease Models, Animal; D000077764:Dronedarone; D004347:Drug Interactions; D004562:Electrocardiography / Q000379:methods; D006329:Heart Conduction System / Q000187:drug effects*; D011817:Rabbits; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D004071:Digitalis Glycosides; D000077764:Dronedarone; D000638:Amiodarone
keywords: Amiodarone; Digitalis; Dronedarone; Ouabain; Therapeutic safety; Ventricular fibrillation