Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction.
The hemodynamic and antiadrenergic effects of dronedarone, a noniodinated compound structurally related to amiodarone, were compared with those of amiodarone after prolonged oral administration, both at rest and during sympathetic stimulation in conscious dogs with a healed myocardial infarction. All dogs (n = 6) randomly received orally dronedarone (10 and 30 mg/kg), amiodarone (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 pressure (MBP), positive rate of increase of left ventricular pressure (+LVdP/dt), echocardiographically assessed left ventricular ejection fraction (LVEF), and fractional shortening (FS), as well as chronotropic response to isoproterenol and exercise-induced sympathetic stimulation were evaluated under baseline and posttreatment conditions. Resting values of LVEF, FS, +LVdP/dt, and MBP remained unchanged whatever the drug and the dosing regimen, whereas resting HR was significantly and dose-dependently lowered after dronedarone and to a lesser extent after amiodarone. Both dronedarone and amiodarone significantly reduced the exercise-induced tachycardia and, at the highest dose, decreased the isoproterenol-induced tachycardia. Thus, dronedarone and amiodarone displayed a similar level of antiadrenergic effect and did not impair the resting left ventricular function. Consequently, dronedarone might be particularly suitable for the treatment and prevention of various clinical arrhythmias, without compromising the left ventricular function.
Djandjighian
L
L
Cardiovascular/Thrombosis Research Department, Sanofi-Synthelabo, Montpellier, France. laurent.djandjighian@sanofi-synthelabo.fr
Planchenault
J
J
Finance
O
O
Pastor
G
G
Gautier
P
P
Nisato
D
D
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000638:Amiodarone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D000077764:Dronedarone; D004452:Echocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000502:physiology
D018674:Adrenergic Antagonists; D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone