Comparative antiarrhythmic efficacy of amiodarone and dronedarone during acute myocardial infarction in rats (Journal article)

Agelaki, M. G./ Pantos, C./ Korantzopoulos, P./ Tsalikakis, D. G./ Baltogiannis, G. G./ Fotopoulos, A./ Kolettis, T. M.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Action Potentials/drug effects,Amiodarone/*analogs & derivatives/pharmacology/*therapeutic use,Animals,Anti-Arrhythmia Agents/pharmacology/*therapeutic use,Disease Models, Animal,Electrocardiography, Ambulatory,Epinephrine/metabolism,Female,Myocardial Infarction/complications/*drug therapy/mortality,Norepinephrine/metabolism,Radioimmunoassay,Random Allocation,Rats,Rats, Wistar,Tachycardia, Ventricular/drug therapy,Telemetry,Thyroid Hormones/metabolism,Ventricular Fibrillation/drug therapy
ISSN: 0014-2999
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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