Abstract
We evaluated antiarrhythmic effects of N-696 using canine digitalis ventricular arrhythmia models and electrophysiological actions of N-696 using canine ventricular muscles and isolated blood perfused A-V node preparations and compared the effects with those of proranolol. 1) N-696 at 30 mg/kg, i.v. was not effective on digitalis arrhythmia, but reduced the total heart rate and atrial rate for 60 min and transiently decreased the blood pressure. Propranolol at 3 mg/kg, i.v. transiently suppressed digitalis ventricular arrhythmia and decreased the total heart rate, atrial rate and blood pressure. The minimum effective plasma concentration of propranolol was 1.7±0.4μg/ml. 2) Ten to 100μg/ml N-696 and 3 to 10μg/ml propranolol did not affect the resting potential and the action potential duration at 75%, repolarization of the canine ventricular muscle, but decreased the maximum rate of rise of the action potential in a dose-dependent fashion, and 100μg/ml N-696 decreased significantly the action potential amplitude. The minimum effective durg concentration of N-696 was 60μg/ml, and that of propranolol was 6μg/ml. 3) N-696 (30μg-3mg) dose-dependently delayed the A-V conduction time of the isolated blood perfused A-V node preparation when it was administered into the posterior septal artery (PSA) and the anterior septal artery (ASA). Propranolol(10-600μg) also had similar effects, but the doses of N-696 delaying the A-V conduction time by 15% was about 8 to 21 times higher than those of propranolol.
