双异丙吡胺对犬右心室心外膜下细胞瞬间外向钾电流抑制作用的研究  

Study on the Inhibition Effect of Disopyramide on the Canine Right Ventricular Epi Cells Transient Outward Potassium Current

作　　者：王立中[1] 杨新春[2] 张银[1] 王金波[1] 曹树军[1] 

机构地区：[1]北京市大兴区人民医院心内科,北京102600 [2]首都医科大学附属北京朝阳医院心脏中心,北京100020

出　　处：《中国医药导刊》2006年第3期208-209,213,共3页Chinese Journal of Medicinal Guide

摘　　要：目的:探讨双异丙吡胺对犬右心室心外膜下(Epi)细胞复极1期末4-氨基吡啶敏感的非钙依赖性瞬间外向钾电流(Ito1)的抑制作用,以期为临床药物治疗Brugada综合征等起源于右心室的恶性心律失常疾病提供必要的证据。方法:酶解分离犬右心室Epi单个心肌细胞,在全细胞钳制条件下,观察双异丙吡胺对犬右心室Epi细胞Ito1离子流的抑制作用。结果: (1)在刺激频率为0．2Hz、37℃和去极化试验电压+70mv水平,在临床相关的治疗浓度范围内双异丙吡胺呈浓度依赖性有效地抑制犬Ito1离子流而无电压依赖性。(2)当刺激频率超过1Hz时,双异丙吡胺对Ito1离子流的抑制作用具有明显的快频率应用依赖性。(3)双异丙吡胺对Ito1离子流的抑制作用依赖于去极化试验电压脉冲提示双异丙吡胺属于通道开放状态阻滞剂。结论:在临床相关的治疗浓度范围内双异丙吡胺能以浓度依赖性方式抑制犬右心室Epi细胞的Ito1离子流,恢复Epi细胞间Ito1离子流的均衡性,因而对Brugada综合征等疾病所致的、以2相折返为基础的恶性心律失常可能有预防作用。Objective： To investigate the inhibition effect of Disopyramide on the 4 - aminopyridine sensitive and calcium - independent transient outward current （Ito 1 ） at the end of repelaxization phrase 1 of canine right ventricular epicardial cells in order to provide the aid for preventing the Brngada syndrome .Methods： Enzymatic dissociation of adult canine single right ventricular epi cell. By use of whole cell patch- clamp technique, we quantitatively studied the inhibition effect of disopyramide on Itol.Results： At 0.2Hz, 37℃, ＋ 70mV depelarizationtest petential, Ourresult showed that disopyramide（ 10mmol/L, 15mmol/Land 2（mmol/L） could significantly reduce the amplitude of hol by the way of concentration - dependent in the range of clinical treatment concentration and no volt - dependent; In addition, disopyramide could also suppress hol by fast frequency - dependent and by use- dependent. Conclusion： Disopyramide could significantly decrease the amplitude of Ito 1 by concentration - dependent in the range of clinical treatment concentration and restore the electrical heteronegeity among canine right ventricular Epi cells. So disopyramide may play an important role in preventing malarrhythmias which based 2 phrase reentry caused by Brugada syndrome etc.

关 键 词：双异丙吡胺 犬右心室 心外膜下细胞 瞬间外向钾电流 

分 类 号：R96[医药卫生—药理学]