title: Antiarrhythmic effects of ethmozin in cardiac Purkinje fibers: suppression of automaticity and abolition of triggering.
abstract: The effects of ethmozin were studied on automatic and triggered impulse initiation in isolated canine cardiac Purkinje fibers using standard microelectrode technique. In driven Purkinje fibers with normal (greater than or equal to -80 mV) maximum diastolic potentials, ethmozin (2-4 mg/l or 4.3-8.6 muM) slightly increased the slope of phase 4 depolarization. However, the rate of normal automatic firing in such fibers was decreased by ethmozin and the threshold (take-off) potential of the pacemaker cells was shifted in the depolarizing direction (toward zero potential). In fibers treated with barium chloride (0.10-0.50 mM), "abnormal automaticity" occurred from maximum diastolic potentials of -38 to -68 MV. Ethmozin (2-4 mg/l) consistently slowed and abolished this abnormal automaticity. This appeared to be associated with a decrease in the rate of diastolic depolarization. When lidocaine, 4 or 10 mg/l (17 or 42 muM), was tested on abnormal automaticity induced by barium, it too was found to decrease the rate of diastolic depolarization and decrease the automatic rate. However, lidocaine never terminated barium-induced abnormal automaticity. Ethmozin also consistently abolished abnormal automaticity in Purkinje fibers taken from the endocardial surface of 24- or 48-h infarct zones. Finally, ethmozin (1-4 mg/l or 2.2-8.6 muM) depressed the amplitude of delayed after depolarizations and terminated triggered activity in Purkinje fibers taken from 24-hr infarct zones. Each of these actions could contribute to the antiarrhythmic effects of ethmozin.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D016293:Moricizine; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology; D010640:Phenothiazines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000889:Anti-Arrhythmia Agents; D010640:Phenothiazines; D016293:Moricizine; D008012:Lidocaine