[Antiarrhythmic effects of pilsicainide hydrochloride and effects on cardiac function and ECG in dogs: comparison with disopyramide].
Antiarrhythmic effects and cardiovascular effects of pilsicainide hydrochloride were compared with those of disopyramide in a canine model of coronary ligation-induced ventricular arrhythmias and anesthetized dogs. Pilsicainide (1.25, 2.5 and 5 mg/kg) and disopyramide (2.5 and 5 mg/kg) decreased the arrhythmic ratio ¿(ventricular arrhythmias/total heart rate) x 100¿ dose-dependently. Pilsicainide at 2.5 and 5 mg/kg and disopyramide at 5 mg/kg suppressed ventricular arrhythmias more than 50%. The effective dose of pilsicainide was lower than that of disopyramide, but the effective plasma concentration of pilsicainide was between 3 and 8 micrograms/ml, which was almost the same as that of disopyramide. In anesthetized dogs, both drugs decreased LV dP/dt max in almost the same concentration-dependent manner. PQ-interval was prolonged by pilsicainide, but not by disopyramide. QRS and QTc were prolonged by both drugs in a concentration-dependent manner. However, the prolongation of QTc by disopyramide was provoked at lower plasma concentrations than by pilsicainide. Because the excessive prolongation of QTc lead to the lethal arrhythmias such as torsades de pointes, pilsicainide may be useful as an injectable antiarrhythmic agent superior to disopyramide.
Hidaka
T
T
Suntory Institute for Medicinal Research & Development, Gunma, Japan.
Inoue
T
T
Komoriya
K
K
Hayashi
Y
Y
Inomata
N
N
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D003331:Coronary Vessels; D004195:Disease Models, Animal; D004206:Disopyramide / Q000008:administration & dosage* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008026:Ligation
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine; C042288:pilsicainide; D004206:Disopyramide