Suppression of ventricular arrhythmias by propafenone, a new antiarrhythmic agent, during acute myocardial infarction in the conscious dog. A comparative study with lidocaine.

The responsiveness of ventricular tachycardia (VT) to propafenone, a new antiarrhythmic agent, was evaluated in the conscious dog during acute myocardial infarction (AMI). AMI was produced in the anesthetized closed-chest dogs with an intracoronary catheter system by permanent occlusion in eight dogs and by 2-hour occlusion followed by reperfusion ofthe left anterior descending coronary artery in eight others. Twenty-four hours after surgery, all dogs in both groups had VTwith similar characteristics (rates of 130-220 beats/min) in the conscious, nonsedated state. Administration of propafenone, 4 mg/kg i.v. over 2 minutes, immediately and completely suppressed VT in seven of the permanently occluded and in all eight dogs in the reperfused group. The duration of propafenone-induced normal sinus rhythm (NSR) was inversely related to the rate of VT. Intravenous infusion of propafenone, 0.2 mg/kg/min, after a 4-mg/kg i.v. bolus maintained NSR for the duration of infusion. Propafenone did not change the mean blood pressure. Lidocaine, as much as 5 mg/kg i.v., was ineffective when the VT rate was greater than 160 beats/min and restored NSR only transiently (3-6 minutes) when the VT rate was less than 160 beats/min in either group (p < 0.001 compared with propafenone). Propafenone, unlike lidocaine, significantly (p < 0.05) increased both cathodal and bipolar diastolic excitability threshold and shifted upward the tail portion of the strength-interval relation of the right ventricle. Propafenone had no effect on the effective refractory period of the right ventricle. Plasma propafenone levels during propafenone-induced NSR and myocardial excitability measurements were 3.2 1.6 gg/ml in the reperfused group and 3.0 1.68 ,tg/ml in the permanently occluded group (mean ± SD) (p > 0.1). We conclude that propafenone is very effective against VT during AMI in the dog, and it may be effective in lidocaine-resistant VT during acute ischemia.