title: 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.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011437:Propylamines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects; D011725:Pyridines; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors
chemical_list: D000889:Anti-Arrhythmia Agents; D011437:Propylamines; D011725:Pyridines; C045930:propisomide; D013327:Strophanthidin; D004206:Disopyramide; C004681:acetylstrophanthidin