Negative chronotropic and inotropic effects of class I antiarrhythmic drugs assessed in isolated canine blood-perfused sinoatrial node and papillary muscle preparations.

The present study was designed to assess the negative chronotropic and inotropic effects of 10 class I antiarrhythmic drugs, using isolated canine blood-perfused sinoatrial node and papillary muscle preparations. Each drug showed negative chronotropic and inotropic effects in a dose-related manner. The potency of the suppressive effect on the sinoatrial automaticity was in the order of aprindine, quinidine, flecainide, lidocaine, mexiletine, cibenzoline, disopyramide, procainamide, tocainide, and phenytoin, while the effect on the ventricular contraction was in the order of aprindine, flecainide, cibenzoline, lidocaine, mexiletine, disopyramide, tocainide, phenytoin, quinidine, and procainamide. The differences in the suppressive effects could not necessarily be explained by their subclassification, based either on action potential duration or kinetic properties of dissociation or association with sodium channels. On the other hand, we found a good correlation between the negative inotropic effects of class I drugs in this study and the canine antiarrhythmic plasma concentrations for the digitalis- and coronary ligation-induced ventricular arrhythmia models in our previous studies. However, the negative chronotropic effects of the drugs showed a poor correlation with the antiarrhythmic plasma drug concentrations. The data shown in this paper may provide a convenient guideline for predicting acute cardiosuppressive effects of antiarrhythmic drugs, especially in patients with reduced cardiac function.