Comparison of cardiovascular effects of a novel class Ic antiarrhythmic agent, NIK-244, with those of flecainide in isolated canine heart preparations cross-circulated with a donor dog.
To assess the cardiovascular effects of a new class I antiarrhythmic agent, NIK-244, and to compare them with those of flecainide, canine isolated, sinoatrial node, papillary muscle and atrioventricular node preparations cross-circulated with a donor dog were used. NIK-244 injected intraarterially into the isolated preparations showed dose-related negative chronotropic, negative inotropic, and coronary vasodilator effects, which are comparable to those of flecainide, and it also showed a dose-related negative dromotropic effect on both atrio-His (AH) and His-ventricular (HV) conduction. The prolongation of AH interval by NIK-244 was significantly more potent than that by flecainide, while that of the HV interval by NIK-244 was slightly more potent, but not significantly, compared with that by flecainide. NIK-244 administered intravenously into the donor dog showed bradycardic and depressor effects in both the donor dog and the cross-circulated sinus node and papillary muscle preparations, which are comparable to the effects of flecainide. Although the negative dromotropic effects of NIK-244 on both the donor dog heart and the cross-circulated atrioventricular node preparation started more slowly, they were more potent and longer-lasting than those of flecainide. Our results suggest that NIK-244 may be a more powerful and longer-lasting antiarrhythmic agent than flecainide, since the antiarrhythmic action of class I drugs is considered to result from inhibition of the fast inward current, which is the most important depolarizing current responsible for the intraatrial and His-Purkinje-ventricular conduction.
Sugiyama
A
A
Department of Pharmacology, Yamanashi Medical College, Japan.
Motomura
S
S
Hashimoto
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003427:Cross Circulation / Q000379:methods; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005424:Flecainide / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000187:drug effects; D010640:Phenothiazines / Q000008:administration & dosage / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D010640:Phenothiazines; C046818:ethacizine; D005424:Flecainide