Related Experiment Video
Updated: Apr 17, 2026

Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine
Published on: July 7, 2016
Dronedarone and digitalis: individually reduced post-repolarization refractoriness enhances life-threatening
Gerrit Frommeyer1, Peter Milberg2, Jochen Schulze Grotthoff2
1Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany gerrit.frommeyer@ukmuenster.de.
Aims:
Interaction between dronedarone and digitalis has been discussed as a possible cause for increased mortality in the presence of dronedarone observed in the PALLAS trial. The aim of this study was to assess possible proarrhythmic effects of dronedarone in combination with digitalis in an experimental whole heart model.
Methods And Results:
Twenty-six female rabbits underwent chronic oral treatment with dronedarone (50 mg/kg/day for 6 weeks). Twenty-four rabbits received placebo. Heart failure was induced by rapid ventricular pacing. Sham-operated rabbits received a right-ventricular pacing lead but were not paced. Thereafter, hearts were isolated and Langendorff-perfused. Monophasic action potentials and a 12 lead electrocardiogram showed a dose-dependent decrease of QT interval, APD90, effective refractory periods, and postrepolarization refractoriness in control hearts and dronedarone-pretreated hearts after application of ouabain (0.1 and 0.2 µM). After acute application of ouabain, ventricular fibrillation (VF) was inducible by programmed ventricular stimulation in 6 of 12 untreated sham hearts (38 episodes) as compared with 7 of 11 dronedarone-pretreated sham hearts (76 episodes). In untreated failing hearts, 6 of 12 hearts were inducible (47 episodes) as compared with 7 of 15 hearts dronedarone-pretreated failing hearts (93 episodes).
Conclusion:
In this study, ouabain treatment resulted in an increased ventricular vulnerability in chronically dronedarone-pretreated control and failing hearts. Ouabain led to a significant abbreviation of ventricular repolarization. This was more marked in dronedarone-pretreated hearts and resulted in an elevated incidence of VF. This may help to interpret the results of the PALLAS trial.
More Related Videos
10:41Laser-Induced Action Potential-Like Measurements of Cardiomyocytes on Microelectrode Arrays for Increased Predictivity of Safety Pharmacology
Published on: September 13, 2022
08:19Electrophysiological Assessment of Murine Atria with High-Resolution Optical Mapping
Published on: February 22, 2018
Related Concept Videos
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers
Heart Failure Drugs: Inotropic Agents
Dysrhythmias VI: Management of Dysrhythmias