CHRONOTROPIC CARDIAC EFFECTS OF FALIPAMIL IN CONSCIOUS DOGS - INTERACTIONS WITH THE AUTONOMIC NERVOUS-SYSTEM AND VARIOUS IONIC CONDUCTANCES

The chronotropic cardiac effects of falipamil were studied in consciou s dogs with chronic atrioventricular (AV) block. Falipamil (0.5-2 mg/k g) initially increased atrial rate dose dependently. After atropine an d atropine-pindolol, falipamil (2 mg/kg) decreased atrial rate, but af ter pindolol, it did not modify atrial rate. After atropine-pindolol-p henoxybenzamine, atropine-pindolol-yohimbine, atropine-pindolol-verapa mil, and atropine-pindolol-quinidine pretreatment, falipamil produced atrial bradycardia. Falipamil dose-relatedly decreased ventricular rat e. Falipamil (2 mg/kg) decreased ventricular rate after atropine, pind olol, and atropine-pindolol more than under basal conditions. After th e other four pretreatments, it also produced ventricular bradycardia. Falipamil did not affect mean blood pressure (MBP) at any -dose. These results (a) show that the initial atrial cardioacceleration produced by falipamil results from its direct vagolytic action; (b) show that a bsence of atrial bradycardia results from buffering by the vagolytic e ffect and/or a relatively low basal atrial rate; (c) suggest that the falipamil ventricular bradycardia is partly buffered by the vagolytic effect, norepinephrine (NE) release, and involvement Of alpha2-adrenoc eptors; (d) exclude involvement of postsynaptic muscarinic, alpha- and beta-adrenoceptors, and of the slow calcium current in the mechanism( s) by which falipamil decreases cardiac automaticity; and (e) suggest possible involvement of a quinidine-sensitive current in this (these) mechanism(s).