Effects of class I antiarrhythmic drugs on the digitalis-induced triggered activity arrhythmia model: a rationale for the short-term use of class I drugs against triggered arrhythmias.
Delayed afterdepolarization (DAD)-induced triggered activity has been considered to be one of the generation mechanisms of ventricular arrhythmias in the presence of intracellular Ca2+ overload. In this study, we analyzed the antiarrhythmic effects of class I antiarrhythmic drugs, namely, disopyramide, procainamide, mexiletine, and flecainide, on a recently developed DAD-induced triggered arrhythmia model, which consists of a canine ventricular septum preparation cross-circulated with a blood-donor dog. After intravenous administration of ouabain to the donor dog, triggered arrhythmias were consistently induced in the cross-circulated preparation by train stimulation (cycle length: 300 ms; train number: 15). Intracoronary administration of disopyramide, procainamide, mexiletine, and flecainide as well as lidocaine suppressed the triggered arrhythmias at clinically relevant doses. Similar doses have been demonstrated to suppress intraventricular conduction in the same experimental model. These results suggest that the Na+ channel inhibition by class I drugs is an effective pharmacological intervention for suppressing Ca2+ overload, which may provide a rationale for the short-term use of class I drugs against the triggered arrhythmias in clinical practice.
Takahara
Akira
A
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan.
Sugiyama
Atsushi
A
Hashimoto
Keitaro
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D005117:Cardiac Complexes, Premature / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D008012:Lidocaine; D008297:Male; D010042:Ouabain; D015222:Sodium Channels / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D010042:Ouabain; D008012:Lidocaine