Evaluation of cardiac vulnerability and antifibrillatory properties of anti-arrhythmic drugs.

A method of evaluating the antifibrillatory properties of drugs by their effect on the acceleration of the cardiac rhythm by electric pulses was developed. It permitted measurement of fibrillation thresholds and the maximal driving frequency of stimulation. The heart was accelerated in closed chest dogs, and this increased the fibrillation thresholds after the application of lidocaine (1 mg/kg), quinidine (5 mg/kg), and novocainamide (15 mg/kg body wt.). The development of an original programmed stimulator increased the accuracy of the method by means of establishing the initial and terminal stimulation rates and observing the constant steps of change of pulse intervals. Four methods of causing fibrillation were compared: (1) a single pulse during the vulnerable phase of the cardiac cycle; (2) a train of pulses overlapping the vulnerable phase; (3) sequential R on T pacing; (4) simple acceleration of the cardiac rhythm. In addition to the other methods, the method of accelerating the heart rate differs in that only a small amplitude of stimulating pulses is needed. The present method may be used in the case of an unstable initial cardiac rhythm.