Conversion of atrial fibrillation by the experimental antiarrhythmic drug tedisamil in two canine models.

Abstract

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.

• Authors: P S Fischbach, T D Barrett, R Goyal, B C Tran, Z A Syed, J K Hennan, B R Lucchesi
• Journal: Journal of cardiovascular electrophysiology (J Cardiovasc Electrophysiol) Vol. 12 Issue 10 Pg. 1138-44 (Oct 2001) ISSN: 1045-3873 [Print] United States
• PMID: 11699522 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Arrhythmia Agents
• Bridged Bicyclo Compounds, Heterocyclic
• Cyclopropanes
• tedisamil

Topics

• Animals
• Anti-Arrhythmia Agents (administration & dosage, therapeutic use)
• Atrial Fibrillation (drug therapy)
• Blood Pressure (drug effects)
• Bridged Bicyclo Compounds, Heterocyclic (administration & dosage, therapeutic use)
• Cyclopropanes (administration & dosage, therapeutic use)
• Disease Models, Animal
• Dogs
• Dose-Response Relationship, Drug
• Electrocardiography
• Heart Rate (drug effects)
• Michigan
• Models, Cardiovascular
• Reaction Time (drug effects)