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

Summary: 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 10-5M) were compared with those of disopyramide phosphate (5 mg/L, 1.4 x 10-5M). CM7857 significantly lowered the maximum rate of rise of phase 0 (Vmax) from 351.5 ± 50.6V7/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 drags.