Comparative antiarrhythmic efficacy of amiodarone and dronedarone during acute myocardial infarction in rats.
The effects of dronedarone, a non-iodinated derivative of amiodarone, on ventricular tachycardia and ventricular fibrillation post-myocardial infarction are not well established. Fifty-five Wistar rats were randomly allocated to a 2-week oral treatment with either vehicle (n=18), amiodarone (30 mg/kg, n=20), or dronedarone (30 mg/kg, n=17). After acute coronary artery ligation, a single-lead electrocardiogram was continuously recorded for 24 h and episodes of ventricular tachycardia/fibrillation as well as mortality rates were analysed. Monophasic action potential recordings were obtained from the left ventricular epicardium at baseline and 24 h post-myocardial infarction. Thyroid hormones and catecholamines were measured using radioimmunoassay. Thyroid function was similar in the 3 groups. Compared to controls, amiodarone and dronedarone equally decreased the number of ventricular tachycardia/fibrillation episodes by approximately 75%. Both agents prevented the increase in monophasic action potential duration and in beat-to-beat variation. Norepinephrine levels were lower only after amiodarone treatment. Despite the observed antiarrhythmic effect, total mortality did not differ between groups (38.8% in controls, 30.0% in the amiodarone group and 58.8% in the dronedarone group), because of excess bradyarrhythmic mortality in both drug groups that reached significance in the dronedarone group. Dronedarone and amiodarone display similar antiarrhythmic efficacy post-myocardial infarction, partly by preventing repolarization inhomogeneity. However, dronedarone increases bradyarrhythmic mortality possibly secondary to its negative inotropic effects.
Agelaki
Maria G
MG
Department of Cardiology, University of Ioannina Medical School, 45110 Ioannina, Greece.
Pantos
Constantinos
C
Korantzopoulos
Panagiotis
P
Tsalikakis
Dimitrios G
DG
Baltogiannis
Giannis G
GG
Fotopoulos
Andreas
A
Kolettis
Theofilos M
TM
D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000077764:Dronedarone; D015716:Electrocardiography, Ambulatory; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D009638:Norepinephrine / Q000378:metabolism; D011863:Radioimmunoassay; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017180:Tachycardia, Ventricular / Q000188:drug therapy; D013686:Telemetry; D013963:Thyroid Hormones / Q000378:metabolism; D014693:Ventricular Fibrillation / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents; D013963:Thyroid Hormones; D000077764:Dronedarone; D000638:Amiodarone; D009638:Norepinephrine; D004837:Epinephrine