In vivo and in vitro antiarrhythmic and arrhythmogenic effects of N-acetyl procainamide.
We studied the effects of N-acetyl procainamide (NAPA) on isolated canine cardiac tissues by using standard microelectrode techniques. NAPA (10-40 mg/l) does not suppress the rate of phase 4 depolarization of Purkinje fibers and does not change resting membrane potential, action potential amplitude or maximum upstroke velocity of phase O of the action potentials of Purkinje fibers or ventricular muscle cells. In contrast, action potential duration of both types of cells is significantly prolonged by NAPA in a dose-dependent manner. In toxic concentrations (80-240 mg/l), NAPA can produce a "secondary plateau" at about -55 mV during phase 3 of the action potential of Purkinje fibers driven at cycle lengths of 2000 to 4000 msec. Early afterdepolarizations and single or multiple spontaneous action potentials were often triggered during the secondary plateau. When NAPA is given to conscious or anesthetized dogs (50-100 mg/kg i.v.), ventricular extrasystoles occur at constant coupling intervals if the basic rate of ventricular activation is slow (60 per minute or slower). Single extrasystoles, or the first extrasystole in a salvo, appear at coupling intervals of 400 to 600 msec. The single and multiple extrasystoles induced by NAPA may be caused by action potentials triggered during the secondary plateau and may degenerate into ventricular fibrillation. In doses of up to 100 mg/kg i.v., NAPA exerts slight antiarrhythmic effects in dogs with 24-hr myocardial infarcts.
D000120:Acecainide / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D006327:Heart Block / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008026:Ligation; D008564:Membrane Potentials / Q000187:drug effects; D011342:Procainamide / Q000031:analogs & derivatives*; D011690:Purkinje Fibers / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D000120:Acecainide; D011342:Procainamide