Effects of phenytoin and quinidine on digitalis-induced oscillatory afterpotentials, aftercontractions, and inotropy in canine ventricular tissues

The object of this study was to compare the electrical and mechanical effects of quinidine and phenytoin on cardiac tissue intoxicated with digitalis. Phenytoin was selected because it is relatively effective against digitalis arrhythmias; quinidine was selected because it is contraindicated in treatment of digitalis arrhythmias. Isolated canine false tendons were exposed to concentrations of acetylstrophanthidin (or actodigin) sufficient to cause oscillatory afterpotentials and aftercontractions. Both phenytoin (1.2 × 10^-5m) and quinidine (1.6 × 10^-6m) decreased the amplitude of oscillatory afterpotentials at various membrane potentials selected by extracellular current application. Quinidine, but not phenytoin, also increased threshold potential. The lowest concentrations of these agents that stopped continuous automatic activity induced in false tendons by trains of rapid stimulation was 7.9 × 10^-6m phenytoin and 1.6 × 10^-6m quinidine. In the absence of digitalis, these concentrations decreased strength of contraction 69.5 (± 13 s.d.) % and 49.6 (± 10 s.d.) %, respectively. Similar concentrations of phenytoin (1.2 × 10^-5m) and quinidine (1.6 × 10^-6m) reduced or abolished oscillatory afterpotentials and aftercontractions induced by digitalis in false tendons. Abolition of aftercontractions eliminated potentiating and depotentiating effects of aftercontractions on superimposed beats and reversed the effects of digitalis on the configuration of the force-frequency relation and course of restitution of contractility. In muscle, studied simultaneously with the false tendons, phenytoin, but not quinidine, decreased strength of contraction. This study demonstrates that phenytoin and quinidine have remarkably similar, but not identical effects on isolated cardiac tissues exposed to digitalis.