Conversion of Atrial Fibrillation by the Experimental Antiarrhythmic Drug Tedisamil in Two Canine Models

• Published in: Journal of cardiovascular electrophysiology 2001-10, Vol.12 (10), p.1138-1144
• Main Authors: FISCHBACH, PETER S., BARRETT, TERRANCE D., GOYAL, RAJIVA, TRAN, BINH C., SYED, ZAFFER A., HENNAN, JAMES K., LUCCHESI, BENEDICT R.
• Format: Article
• Language: English
• Subjects: animal model; Animals; Anti-Arrhythmia Agents - administration & dosage; Anti-Arrhythmia Agents - therapeutic use; antiarrhythmic drugs; atrial fibrillation; Atrial Fibrillation - drug therapy; Blood Pressure - drug effects; Bridged Bicyclo Compounds, Heterocyclic - administration & dosage; Bridged Bicyclo Compounds, Heterocyclic - therapeutic use; Cyclopropanes - administration & dosage; Cyclopropanes - therapeutic use; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Electrocardiography; Heart Rate - drug effects; Michigan; Models, Cardiovascular; Reaction Time - drug effects; tedisamil
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1046/j.1540-8167.2001.01138.x

Tedisamil Conversion of AF in Two Canine Models. Introduction: Tedisamil is an experimental bradycardic agent possessing action potential‐prolonging effects. It has been proven effective in terminating ventricular arrhythmias in several animal models and atrial flutter in a conscious dog model. There are no reports to date evaluating tedisamil's efficacy in terminating atrial fibrillation (AF). Methods and Results: Two different canine models of AF were used. One group of dogs (n = 6) was subjected to 28 days of chronic fibrillatory pacing at 50 Hz using an implantable neural stimulator. Sustained AF was achieved in all dogs within 14 days of initiating pacing. A second set of dogs (n = 5) had AF induced via bilateral vagal stimulation. Tedisamil 1 mg/kg was 100% effective in terminating AF in both models. Cardioversion was associated with a statistically significant prolongation of the fibrillatory cycle length immediately before return to normal sinus rhythm in both models. A dose‐response trial was performed in the vagal AF group as well as in a second group of three dogs that underwent chronic fibrillatory pacing. The efficacy of tedisamil was dose dependent, with limited efficacy at 0.1 and 0.3 mg/kg intravenously in both models. Tedisamil was able to prevent reinduction of sustained AF 30 minutes after administration of 1 mg/kg in the chronic pacing model in all dogs. Side effects included minor hypersalivation in most dogs receiving the 1 mg/kg dose. No ventricular ectopy or arrhythmias were observed. Conclusion: Tedisamil is effective for conversion of sustained AF to normal sinus rhythm in two different models of AF.