抗心律失常药UK－68798对家兔心脏房室结区不同细胞的电生理作用  

ELECTROPHYSIOLOGICAL EFFECTS OF ANTIARRHYTHMIC DRUG UK-68798 ON DIFFERENT AV NODAL CELLS IN RABBIT HEART

作　　者：高天礼[1] Beye.,T 

机构地区：[1]北京大学生物系生理教研室

出　　处：《生理学报》1994年第3期258-266,共9页Acta Physiologica Sinica

摘　　要：在离体家兔ＡＶＮ区标本上，用微电极技术研究了Ⅲ类抗心律失常新药ＵＫ－６８７９８对ＡＮ，Ｎ，ＮＨ，Ｈ４种细胞的电生理效应。浓度５×１０－９至５×１０－６ｍｏｌ／Ｌ的ＵＫ－６８７９８对４种细胞的动作电位幅值（ＡＰＡ）、静息膜电位（ＲＰ）皆无影响。对ＡＶＮ的自搏率有剂量依赖性减慢作用，但不改变Ａ－Ｈ传导时间。在５×１０－８－５×１０－６ｍｏｌ／Ｌ剂量范围，此药使动作电位时程（ＡＰＤ５０）和（ＡＰＤ９０）发生剂量依赖性延长。４种细胞中以Ｎ细胞的ＡＰＤ５０和ＡＰＤ９０延长百分率最高。各种细胞ＡＰＤ９０延长百分率的排列次序为Ｎ＜ＡＮ＜Ｈ＜ＮＨ，当浓度为５×１０－６ｍｏｌ／Ｌ时的延长百分率分别为９５±２６％（Ｎ），７５±２２％（ＡＮ），６３±２６％（Ｈ），４６±２６％（ＮＨ）。在ＵＫ－６８７９８的作用下，４种细胞的有效不应期（ＥＲＰ）也发生剂量依赖性延长，但不存在像ＡＰＤ延长百分率那样的差别。此外，４种细胞ＥＲＰ所相当的复极化膜电位未受药物影响，从而避免了由于兴奋性恢复的不均一性，使ＡＶＮ区成为折返性心律失常的发源地．By means of microelectrode techniques the electrophysiological effects of a newclass Ⅲ antiarrhythmic agent, UK-68798 (Dofetilide), were investigated on atrionodal (AN),nodal (N), nodal-His (NH) and His (H) cells in the AVN area of rabbitheart. UK-68798 (5 × 10-9 to 5 × 10-6 mol/L ) had no effect on APA and RP of the4 kinds of cells but caused a dose-dependent decrease in AVN spontaneous rhythm without changing the A-H conduction time. APD50 and APD90 were prolonged markedly bythe drug in a dose-dependent manner. Among the 4 kinds of cells, N cell had the highest percentage increment in APD, indicating a prominent sensetivity to the drug. Forexample, at 5×10-6 mol/L, the prolongation percentages of APD90 are:95±26%(N),75±22% (AN), 63± 26 % (H), 46± 26% (NH).The effective refractoryPeriods(ERP) of the 4 kinds of cells were lengthened also in a dose-dependent manner,while the ERP increment percentages (△ERP% ) of the 4 kinds of cells did not showsignificant difference. However,ERP corresponding repolarization membrane potentials (ERP-RMP) of the 4 kinds of cells were not affected by the drug.The above results suggested that though ERP increased in parallel with APD prolongation,the homogeneous△ERP% and unchanged ERP-RMP values of the 4 kinds of cellls would prevent the AVN area from becoming a source of reentry arrhythmias under the action ofUK-68798.

关 键 词：房室结 动作电位时程 抗心律失常药 

分 类 号：R972.2[医药卫生—药品]