Evaluation of antifibrillatory effects of drugs

Several electrical stimulation techniques have been used to measure ventricular fibrillation (VF) threshold such as single pulse stimulation, train of pulses stimulation, continuous 50-Hz stimulation and sequential pulse stimulation. This study was undertaken to clarify the difference in VF threshold values obtained by each method. The development of VF was classified into 4 stages. Stage 1 is the phase in which fragmented activities are generated at the stimulated area of the ventricular muscle. In stage 2, the local activities propagate to surrounding ventricular muscle, causing ventricular excitation. Stage 3 is characterized by repetitive ventricular excitations. In state 4, repetitive ventricular responses in a form of accelerating tachycardia induce disorganized excitations that finally degenerate into fibrillation. Based on this classification of stages between local excitation and fibrillation, single pulse stimulation is considered to measure VF threshold for stages 1 to 4, continuous 50-Hz stimulation for stages 2 to 4 and sequential pulse stimulation for stages 3 and 4. Thus, the antifibrillatory effect of drugs can be interpreted with some significance by using different stimulation methods. The sequential pulse stimulation method revealed that some antiarrhythmic agents caused a dissociation between repetitive nonstimulated excitation (RE) threshold and VF threshold. Procainamide and disopyramide increased RE threshold while decreasing VF threshold. Mexiletine and lidocaine elevated both RE and VF thresholds. Local infusion of procainamide at the site of test stimulation reduced both thresholds. However, after the application of procainamide to the whole heart, RE threshold remained decreased but VF threshold was elevated. It is likely that the antifibrillatory effect of the drug includes 2 different processes: antireentrant and antimultiple reentrant effects.