Comparison of cardiovascular effects of pirmenol with those of disopyramide in isolated canine heart preparations cross-circulated with a donor dog.
To assess the cardiovascular profiles of pirmenol, a new antiarrhythmic drug, and to compare them with those of disopyramide, isolated canine sinoatrial node, papillary muscle and atrioventricular node preparations cross-circulated with a donor dog were used. Pirmenol injected intraarterially into the isolated preparations showed negative chronotropic and inotropic effects, which were comparable to those of disopyramide; and it also showed coronary vasodilator and negative dromotropic effects on atrio-His as well as His-ventricular conduction, which were significantly more potent than those of disopyramide. Similarly, pirmenol administered intravenously into the donor dog showed more potent negative dromotropic effects on the PQ interval and QRS width than disopyramide, while in the isolated preparations cross-circulated by the donor dog, pirmenol and disopyramide showed equipotent cardiodepressant effects. In the same preparation, pirmenol decreased coronary blood flow following a transient increase, while disopyramide only decreased coronary blood flow. Since the antiarrhythmic action of class I drugs is considered to result from inhibition of the fast inward current, which generates and propagates action potentials and also induces ventricular automaticity, our results suggest that pirmenol possesses an electrophysiologic effect typical to an efficacious class I agent such as disopyramide.
Sugiyama
A
A
Department of Pharmacology, Yamanashi Medical College, Japan.
Motomura
S
S
Tamura
K
K
Hashimoto
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003427:Cross Circulation; D004206:Disopyramide / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects
D010880:Piperidines; D004206:Disopyramide; C024318:pirmenol