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

Abstract

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 8 dogs and by 2-h occlusion followed by reperfusion of the left anterior descending coronary artery in 8 others. At 24 h after surgery, all dogs in both groups had VT with similar characteristics (rates of 130-220 beats/min) in the conscious, nonsedated state. Administration of propafenone, 4 mg/kg i.v. over 2 min, immediately and completely suppressed VT in 7 of the permanently occluded and in all 8 reperfused dogs. The duration of propanfenone-induced normal sinus rhythm (NSR) was inversely related to the rate of VT. I.v. infusion of propafenone, 0.2 mg/kg per 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 > 160 beats/min and restored NSR only transiently (3-6 min) when the VT rate was < 160 beats/min in either group (P < 0.001 compared with propafenone). Propafenone, unlike lidocaine, signficantly (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. Propanfenone 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 .mu.g/ml in the reperfused group and 3.0 .+-. 1.68 .mu.g/ml in the permanently occluded group (mean .+-. SD) (P < 0.1). Apparently, propafenone is very effective against VT during AMI in the dog, and it may be effective in lidocaine-resistant VT during acute ischemia.