Effects of antiarrhythmic drugs on canine ventricular arrhythmia models: which electrophysiological characteristics of drugs are related to their effectiveness?
In order to compare and clarify the effects of various antiarrhythmic drugs when given as monotherapy, we reevaluated our previous data on antiarrhythmic drugs and recalculated antiarrhythmic plasma concentrations of drugs for several canine arrhythmia models. We used three spontaneously occurring arrhythmias: a) digitalis-, b) two-stage coronary ligation-, and c) adrenaline-induced arrhythmias. All antiarrhythmic drugs of class I suppressed digitalis arrhythmia, and, except for lidocaine, also suppressed coronary ligation arrhythmia. Class II antiarrhythmic drugs, beta blockers, and class IV antiarrhythmic drugs, Ca antagonists, had common features of effectiveness and suppressed adrenaline arrhythmia in relatively low concentrations. Class III drugs were not effective on these three arrhythmias. Differences among the antiarrhythmic effects of class I drugs could not be explained by their subclassification based either on action potential duration or kinetic properties of dissociation or association with Na channels. New triggered arrhythmia models in vivo and in vitro canine hearts were developed, and drug effects were not the same as those on the three spontaneously occurring arrhythmia models.
Hashimoto
K
K
Department of Pharmacology, Yamanashi Medical College, Japan.
Haruno
A
A
Matsuzaki
T
T
Sugiyama
A
A
Akiyama
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000145:classification / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D004074:Digitoxin / Q000037:antagonists & inhibitors; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles; D006801:Humans; D008297:Male; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D004074:Digitoxin