Electrophysiologic effects of AHR 10718 on isolated cardiac tissues.
We used microelectrode and blood superfusion techniques to study the electrophysiologic effects of a new antiarrhythmic compound, AHR 10718 (N'-(2-(diethylamino)ethyl)-N-(1-methylethyl)-N-(2-(phenylsulfonyl )ethyl)urea,(Z)-butanedioate) on the electrophysiologic properties of canine Purkinje fibers and papillary muscles. AHR 10718 (greater than or equal to 5 X 10(-6) M) induced a use-dependent decrease in Vmax and significantly decreased Purkinje fiber conduction velocity and action potential duration. In addition, membrane responsiveness was depressed and the effective refractory period shortened. The effects of AHR 10718 were not highly dependent on [K+]0. Vmax of ventricular muscle action potentials also was reduced. However, in contrast to Purkinje fibers, ventricular muscle action potentials were significantly prolonged by AHR 10718 (greater than or equal to 5 X 10(-6) M). AHR 10718 had no effect on slow response action potentials induced by isoproterenol and high [K+]0. AHR 10718 significantly decreased normal automaticity, catecholamine-enhanced automaticity, and abnormal automaticity induced by barium or myocardial infarction. It also suppressed triggered activity and reduced delayed afterdepolarization amplitude in ouabain-treated Purkinje fibers and infarcted myocardium. These studies suggest that AHR 10718 may be effective against arrhythmias resulting from conduction disturbances and certain forms of abnormal impulse initiation.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D010671:Phenylurea Compounds; C045188:AHR 10718; D011188:Potassium