Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction

The hemodynamic and antiadrenergic effects of dronedarone, a noniodinated c ompound structurally related to amiodarone, were compared with those of ami odarone after prolonged oral administration, both at rest and during sympat hetic stimulation in conscious dogs with a healed myocardial infarction. Al l dogs (n = 6) randomly received orally dronedarone (10 and 30 mg/kg), amio darone (10 and 30 mg/kg), and placebo twice daily for 7 days, with a 3-week washout between consecutive treatments. Heart rate (HR), mean arterial pre ssure (MBP), positive rate of increase of left ventricular pressure (+LVdP/ dt), echocardiographically assessed left ventricular ejection fraction (LVE F), and fractional shortening (FS), as well as chronotropic response to iso proterenol and exercise-induced sympathetic stimulation were evaluated unde r baseline and posttreatment conditions. Resting values of LVEF, FS, +LVdP/ dt, and MBP remained unchanged whatever the drug and the dosing regimen, wh ereas resting HR was significantly and dose-dependently lowered after drone darone and to a lesser extent after amiodarone. Both dronedarone and amioda rone significantly reduced the exercise-induced tachycardia and, at the hig hest dose, decreased the isoproterenol-induced tachycardia. Thus, dronedaro ne and amiodarone displayed a similar level of antiadrenergic effect and di d not impair the resting left ventricular function. Consequently, dronedaro ne might be particularly suitable for the treatment and prevention of vario us clinical arrhythmias, without compromising the left ventricular function .