Effects of CM7857, a Derivative of Disopyramide, on Electrophysiologic Properties of Canine Purkinje Fibers and Inotropic Properties of Canine Ventricular Muscle

Abstract

Effects of CM7857 on electrophysiologic properties in canine Purkinje fibers and inotropic effects in canine ventricular muscle were studied. As CM7857 is a derivative of disopyramide phosphate, the effects of CM7857 (5 mg/L, 1.5 X 10(-5) M) were compared with those of disopyramide phosphate (5 mg/L, 1.4 X 10(-5) M). CM7857 significantly lowered the maximum rate of rise of phase 0 (Vmax) from 351.5 +/- 50.6 V/s (mean +/- SE, n = 5) to 283.6 +/- 33.0 V/s, and conduction velocity from 2.68 +/- 0.56 m/s to 1.70 +/- 0.28 m/s. The automaticity of Purkinje fibers was depressed by CM7857 as the result of reduction in the slope of phase 4. These effects were comparable to those of disopyramide. A marked difference between CM7857 and disopyramide was observed in the effect on action potential duration. APD90 was significantly shortened from 327.4 +/- 14.8 ms (n = 8) to 279.9 +/- 12.9 ms by CM7857, whereas disopyramide did not show any significant changes in APD90. As the CM7857-induced shortening of APD disappeared in low [Na+]o or low [K+]o concentration, it may be attributed to the lowering effect of "window current," a steady-state sodium current, maintaining action potential plateau. Effective refractory period (ERP) did not show any significant change. An acetylstrophanthidin-induced oscillatory afterpotential was significantly depressed by disopyramide, but not by CM7857. Isotonic contraction and isometric contraction of the right ventricular trabecullae were depressed by both drugs.