依布利特对兔左心室肌细胞钠离子通道跨壁异质性的影响

Effects of Ibutilide on Ⅰ_(Na) Current Heterogeneity in Isolated Left Ventricular Myocytes in Rabbits

目的探讨依布利特抗室性心律失常作用的离子机制。方法利用酶解的方法分离出新西兰纯种大耳白兔(体重2.0～2.5kg)心外膜、心内膜和中层心室肌细胞。将各层细胞按处理试剂分为正常对照组、依布利特A(10-7mol/L)组、依布利特B(10-6mol/L)组。应用膜片钳全细胞记录方法,记录各层心室肌细胞钠通道电流(INa)活性的变化,并与正常对照组心肌细胞进行比较分析。结果3组间的中层心肌细胞INa电流I-V曲线差异有统计学意义(P<0.05);对照组与依布利特组的心内膜下细胞INaI-V差异有统计学意义(P<0.01),依布利特A、B组间无显著差异(P>0.05);对照组与依布利特两组心外膜下细胞INaI-V差异有统计学意义(P<0.05),依布利特A、B组间无差异(P>0.05)。依布利特两组与对照组中层心室肌细胞ⅠNa稳态失活曲线比较差异有统计学意义(P<0.05),依布利特A、B组间无显著差异(P>0.05);3组间心内膜下细胞ⅠNa稳态失活曲线差异有统计学意义(P<0.05);对照组与依布利特两组间的心外膜下细胞ⅠNa稳态失活曲线差异有统计学意义(P<0.01),依布利特两组间无显著差异(P>0.05)。依布利特两组与对照组内、中、外3层比较ⅠNa失活后恢复曲线在45、95和145ms时,差异有统计学意义(P<0.05),依布利特两组间各层比较差异也有统计学意义(P<0.05)。结论依布利特使ⅠNaI-V曲线及ⅠNa峰值电流密度下降,稳态失活曲线左移,失活后再恢复时间延长,且高浓度依布利特对心肌细胞钠离子通道的抑制作用强于低浓度。

Objective To explore the mechnisms of lbutilide in ventrieular arrhythmias by studying Ibulide effect on INa heterogeneity of three types of rentricular myocytes. Methods Healthy Newzealand white rabbits weighing 2. 0 to 2.5 kg were selected. The three types of myocytes were isolated enzymologically from the left ventricular wall. The INa inepicardial, endocardial and midmyocardial ceils were recorded by patch clamp techniques in the whole-cell configuration from the three cellular subtypes of the left ventricular free wall. Different solutions of Ibutilide were used： Group A （10^-7mol/L）and group B（ 10^-6 mol/L）. The data were analyzed with one-way analysis of variance （ANOVA） by SPSS 10. 0 software package. Results INaⅠ-Ⅴ curves： Comparison of the Peak Ivo current density of M cell among the three groups showed significant differences between every two groups （P 〈 0. 05） ; Comparison of the Peak INa current density of Endo cell among the three groups showed differences between the normal group and Ibutilide groups （ P 〈 0.05 ）. In the two Ibutilide groups there was no diference （P 〉 0.05） ; Comparison of the Peak INa current density of Epi cell among the three groups showed similar results with that of Endo cell. The INa steady-state inactivation curves： Comparison of the INa steadystate inactivation curves of M cells among the three groups showed differences between the normal group and Ibutilide groups （ P 〈 0.01 ）. In the two Ibutilide groups there was no difference （ P 〉 0.05 ） ; Comparison of the INa steady-state inactivation curves of Endo ceils among the three groups showed differences between each two groups （ P 〈 0. 05 ） ; Comparison of the curves of Epi cells among the three groups showed differences between the normal group and Ibutilide groups（ P 〈 0.01 ）. In the two Ibutilide groups there was no difference （P 〉 0.05）. The INa recovery from inactivation curves ： Comparison of the INa recovery, from inactivation curves at 45, 95,145 ms of M, Endo and Epi cells among three groups in turn showed differences between each two groups （P 〈 0.05）. Conclusion Ibutilide can sigificantly suppress the heterogeneity of Epi, M and Endo. The effects of Ibutilide on left ventricular myocardial are concentration-dependent. Under certain conditions,a higher concentration of Ibutilide can suppress sodium current to a greater extent.