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J Cardiovasc Electrophysiol ; 12(10): 1138-44, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11699522

RESUMO

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.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Ciclopropanos/uso terapêutico , Animais , Antiarrítmicos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Ciclopropanos/administração & dosagem , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Eletrocardiografia , Frequência Cardíaca/efeitos dos fármacos , Michigan , Modelos Cardiovasculares , Tempo de Reação/efeitos dos fármacos
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