ANTIARRHYTHMIC DRUGS AND IN VIVO MYOCARDIAL EXCITABILITY IN THE DOG

1. It has been demonstrated in an earlier study that the threshold for capturing the canine ventricle in situ varies at each time interval during the relative refractory period with a wide range of current levels. Thus, there is no single threshold curve, as is commonly accepted, but rather a range defined by upper limit of threshold (T_U) and a lower limit (T_L). T_U is the minimal current level which always produced a generalized ventricular response. A wide range of lesser current levels produced a local response but with inconsistent propagation throughout the ventricle. T_L is the maximal current level which was never able to elicit a generalized response. 2. Applying the method used for the determination of these limits, the present study was undertaken to characterize the effect of quinidine, lignocaine, procainamide and verapamil in therapeutic doses on T_U and T_L. 3. It was found that quinidine, lignocaine and procainamide elevated T_U and T_L during the relative refractory period, but only quinidine did so during diastole as well. Verapamil, however, did not have any significant influence on excitability. Procainamide had the least effect on the absolute refractoriness of the ventricular muscle as judged by the rightward displacement of the T_U and T_L curves, while quinidine and lignocaine exhibited a significant displacement regarding T_U but much less so for T_L. 4. The proposition is entertained that T_L represents true local excitability of the ventricular muscle and T_U represents the stimulus needed for propagation throughout the heart during the most unfavourable conditions for such spread. 5. Relative changes of T_U/T_L as a function of T_U are considered to express the capability of the locally induced potential to evoke a generalized response: quinidine diminished, procainamide increased, and lignocaine had no effect on this parameter.