Fischbach P S, Barrett T D, Goyal R, Tran B C, Syed Z A, Hennan J K, Lucchesi B R
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
J Cardiovasc Electrophysiol. 2001 Oct;12(10):1138-44. doi: 10.1046/j.1540-8167.2001.01138.x.
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).
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.
Tedisamil is effective for conversion of sustained AF to normal sinus rhythm in two different models of AF.
替地沙米是一种具有延长动作电位作用的实验性心动过缓药物。已证实在几种动物模型中它能有效终止室性心律失常，在清醒犬模型中能终止心房扑动。迄今为止，尚无评估替地沙米终止心房颤动（AF）疗效的报告。
使用了两种不同的犬AF模型。一组犬（n = 6）使用植入式神经刺激器以50 Hz进行28天的慢性颤动起搏。在起搏开始后的14天内，所有犬均实现了持续性AF。第二组犬（n = 5）通过双侧迷走神经刺激诱发AF。在两种模型中，1 mg/kg的替地沙米终止AF的有效率均为100%。在两种模型中，复律均与恢复正常窦性心律前颤动周期长度的统计学显著延长相关。在迷走神经介导的AF组以及另一组接受慢性颤动起搏的3只犬中进行了剂量反应试验。替地沙米的疗效呈剂量依赖性，在两种模型中，静脉注射0.1和0.3 mg/kg时疗效有限。在慢性起搏模型中，所有犬在给予1 mg/kg替地沙米30分钟后均能预防持续性AF的再次诱发。副作用包括大多数接受1 mg/kg剂量的犬出现轻微流涎。未观察到室性早搏或心律失常。
在两种不同的AF模型中，替地沙米可有效将持续性AF转为正常窦性心律。
