Kaverina N V, Berdjajev S J, Darinskij N V
Pharmazie. 1985 Dec;40(12):840-4.
The action of GS 015, a substance out of the series of the novel 5-(dialkyl-amino-acyl)-3-carbalkoxyamino-10,11-dihydro-5H-dibenz[b ,f]azepines, on the alteration of the bioelectric activity in the sympathetic nerves of the heart in case of disturbed cardiac rhythm and ventricular fibrillation was tested on anaesthetized cats. The arrhythmias were induced by two different methods: Artificial electric induction by high-frequency electrical stimulation of the ventricles, occlusion and reperfusion of the anterior descending branch of the arteria coronaria sinistra. GS 015 decreases the tonic bioelectric activity in the sympathetic nerves of the heart and prevents their activation in case of disturbed rhythm which is provoked or by electric stimulation or by occlusion of the coronary artery. With an electric stimulation of the ventricles GS 015, given at doses of 0.5, 1.0, and 2.0 mg/kg, decreases the maximally reproducible frequency in dependence on the dose, which corresponds to an increase of the effective refractory period. At the same time the fibrillation threshold of the ventricles is enhanced in a very intense and long-lasting manner excelling considerably the action of the reference preparations Ethmozin and lidocaine. It may be concluded from the present results that the antiarrhythmic and antifibrillatory effects of GS 015 are basing not only on its immediate action on the myocardial cell but also on a decrease of the activity in the sympathetic nerves of the heart.
在麻醉猫身上测试了新型5 -(二烷基氨基酰基)- 3 - 烷氧羰基氨基 - 10,11 - 二氢 - 5H - 二苯并[b,f]氮杂䓬系列中的一种物质GS 015对心律失常和心室颤动时心脏交感神经生物电活动改变的作用。心律失常通过两种不同方法诱发:通过高频电刺激心室进行人工电诱导,以及左冠状动脉前降支的闭塞和再灌注。GS 015降低心脏交感神经的紧张性生物电活动,并在由电刺激或冠状动脉闭塞引发的节律紊乱情况下防止其激活。在心室电刺激时,以0.5、1.0和2.0mg/kg的剂量给予GS 015,可根据剂量降低最大可重复频率,这对应于有效不应期的延长。同时,心室的颤动阈值以非常强烈和持久的方式提高,大大超过参比制剂乙吗噻嗪和利多卡因的作用。从目前的结果可以得出结论,GS 015的抗心律失常和抗纤颤作用不仅基于其对心肌细胞的直接作用,还基于心脏交感神经活动的降低。