M. Boucher et al., CHRONOTROPIC CARDIAC EFFECTS OF FALIPAMIL IN CONSCIOUS DOGS - INTERACTIONS WITH THE AUTONOMIC NERVOUS-SYSTEM AND VARIOUS IONIC CONDUCTANCES, Journal of cardiovascular pharmacology, 23(4), 1994, pp. 569-575
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).