[Comparative study of different classes of anti-arrhythmia agents on the vulnerability of ischemic ventricular...

A comparative study of the various classes of antiarrhythmic drugs as agents protecting against ischaemia-induced ventricular fibrillation was undertaken in the pig in situ heart, in anaesthetized animals which were subjected to complete temporary occlusion of the left anterior descending coronary artery. This occlusion resulted in fibrillation after a time which varied in inverse ratio to vulnerability to fibrillation. However, as this time did not exceed a few minutes, time to onset of fibrillation could be repeatedly measured in the course of an experiment, in the absence or in the presence of an antiarrhythmic drug. Under ventricular pacing at a constant rate, 180 beats/min, all the class I antiarrhythmic drugs, flecainide, disopyramide and lidocaine, in clinical dose range, reduced time to fibrillation to a large extent (25 to 50%) at the maximum of their action, with gradual return to control values within less than one hour. The enhancement of vulnerability to fibrillation was accompanied by reduction in intraventricular conduction velocity and fibrillation rate. With the same ventricular pacing, no change was observed in time to fibrillation under the influence of propranolol or amiodarone. As for verapamil, it lengthened this time considerably, up to 600%. However, bradycardia produced in usual circumstances ensures a real protection against ischaemic fibrillation with propranolol and amiodarone and enhances protection directly exerted by verapamil.