title: In vitro effects of acute amiodarone and dronedarone on epicardial, endocardial, and M cells of the canine ventricle.
abstract: Amiodarone (AM) is an antiarrhythmic agent widely used in the treatment of ventricular and supraventricular arrhythmias. Dronedarone (DR) is a new compound with a pharmacological profile similar to that of AM, but iodine free. We previously demonstrated that chronic AM treatment reduces transmural dispersion of repolarization (TDR) in the canine heart. We used standard microelectrode technique to evaluate the effects of acute AM (100 microM) and DR (30 microM) on epicardial (EPI), endocardial (ENDO), and M region tissues obtained from the left ventricular wall of the canine heart. Amiodarone (100 microM, 120 min of exposure) produced little change in the action potential duration of ENDO and EPI tissues, but it shortened the action potential of M cells, especially at slow rates, leading to a decrease in TDR. Similar results were observed with DR. Acute AM (100 microM) and DR (30 microM) eliminated d-sotalol-induced early afterdepolarizations (EADs) and triggered activity in 3 of 3 and 2 of 6 M cell preparations, respectively. The reduction of TDR and the elimination of EAD-induced triggered activity differentiates AM and DR from other class III agents. These effects may explain the efficacy and low arrhythmogenicity of acute AM and suggest a potential safe use of DR as an antiarrhythmic agent.
authors.affiliation: Laboratorio de Electrofisiología Celular División Cardiología, Hospital Ramos Mejía, Buenos Aires, Argentina.
authors.forename: Sandra
authors.initials: S
authors.lastname: Moro
authors.forename: Marcela
authors.initials: M
authors.lastname: Ferreiro
authors.forename: Daniela
authors.initials: D
authors.lastname: Celestino
authors.forename: Emiliano
authors.initials: E
authors.lastname: Medei
authors.forename: Marcelo V
authors.initials: MV
authors.lastname: Elizari
authors.forename: Serge
authors.initials: S
authors.lastname: Sicouri
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs; D000077764:Dronedarone; D004699:Endocardium / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology*; D010496:Pericardium / Q000187:drug effects* / Q000502:physiology; D013015:Sotalol / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D013015:Sotalol; D000077764:Dronedarone; D000638:Amiodarone