Electrophysiologic effects of alprafenone on canine cardiac tissue.
We studied the actions of the propafenone derivative alprafenone on transmembrane action potentials (APs) of canine Purkinje fibers (PF) and ventricular and atrial muscle. In PF with normal maximum diastolic potentials (MDPs), alprafenone (5 x 10(-8)-1 x 10(-6) M) produced concentration-dependent decreases in AP amplitude (APA), Vmax, AP duration (APD), and conduction velocity. The effects on Vmax were use dependent. The decrease in PF APD was the result of the drug's action on the slope of phase 2. In contrast to its effect on PF, alprafenone induced a significant increase in APD in ventricular epicardial and endocardial muscle and had no effect on atrial APD. In PF, alprafenone prolonged the effective refractory period (ERP) with respect to APD, and at high [K+]0, prolonged refractoriness beyond repolarization. Alprafenone decreased Vmax and slow-response APA. It had no effect on normal automaticity or isoproterenol (ISO)-induced automaticity, but significantly suppressed BaCl2-induced abnormal automaticity at low levels of membrane potential. Alprafenone inhibited both early and delayed afterdepolarizations and eliminated triggered activity. We conclude that alprafenone's range of actions is consistent with that of other effective antiarrhythmic drugs and is very similar to that of propafenone.
Anyukhovsky
E P
EP
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Rosen
M R
MR
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D011427:Propiophenones / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D011427:Propiophenones; C076009:alprafenone; D007545:Isoproterenol