利多卡因对家兔左右心室外膜心肌细胞电不均一性的影响

Effects of Lidocaine on Cardiac Electrical Heterogeneity of Left and Right Subepicardial Myocytes in Ventricular Walls of Rabbits

目的:探讨利多卡因对家兔左、右心室心外膜心肌细胞动作电位和钠电流(INa)的影响,阐明利多卡因引起左、右心室心外膜心肌细胞电不均一性机制。方法:酶解法分离家兔单个左、右心室心外膜心肌细胞,全细胞膜片钳技术记录左、右心室心外膜心肌细胞动作电位和INa在应用利多卡因前后变化。结果:在电流钳制下,对照组中的左、右心室心外膜心肌细胞上记录动作电位都具有典型的0至4期的形态,2相平台期有心外膜心肌细胞特有的穹窿样凸起;但在利多卡因组,左、右心室心外膜心肌细胞动作均明显地失去2相平台期穹窿样凸起和高度,右室心外膜心肌细胞动作电位失去2相平台期立即复极,形似三角形,左、右心室心外膜心肌细胞动作电位的幅度(APA)和复极化50%和90%(APD50和APD90)均明显减少(P<0.05),且右室心外膜心肌细胞的APA和APD50以及APD90受利多卡因影响后减小最为严重(P<0.05或0.01)。通过电压钳制方式,利多卡因使左、右心室心外膜心肌细胞的INa在各个指令电位下明显减小,而且右室心外膜心肌细胞INa减小的幅度要显著强于左室心外膜心肌细胞INa的减小幅度,当钳制电压为-20mV时,左、右心室心外膜心肌细胞的INa分别由(62.1±4.5)和(54.2±2.9)减小为(40.8±3.2)和(26.5±2.1)(P<0.05或0.01)。利多卡因还使左、右心室心外膜心肌细胞INa的I-V曲线明显上抬,尤其是使右室心外膜心肌细胞INa的I-V曲线处在其他曲线最上面,同时引起左、右心室心外膜心肌细胞的INa电流密度的最大峰值由-20mV略向右偏为-10mV。结论:利多卡因可以引起左、右心室心外膜心肌细胞电不均一性,其可能原因是利多卡因对右室心外膜心肌细胞动作电位和INa的影响程度明显强于左室相同情况。

Objective： To investigate the effects of lidocaine on action potential（AP） and sodium current（INa） of left and right subepicardial myocytes in ventricular walls of rabbits.Methods： The subepicardial myocytes were obtained by enzymatic dissociation in left and right ventricular walls of rabbits.AP and INa were recorded via whole-cell patch-clamp technique in control group and lidocaine group.Results： According to current clamp protocol,APs which were recorded in subepicardial myocytes of both left and right ventricular walls were consisted of five phases from upstroke to phase four,and attached to a dome in the second plateau of the APs in control group,which was the typical characteristics of the APs of subepicardial myocytes of ventricular wall.But lidocaine could delete the dome of the second plateau and degrade the amplitude of the APs of subepicardial myocytes of left and right ventricular walls.It is special differences that APs of the right subepicardial myocytes didn＇t have the second plateau and shaped an acute triangle.AP amplitude（APA） was significantly cut down and APD50 and APD90 were shorted in subepicardial myocytes of left and right ventricular walls with administrating lidocaine（compared with control group,P0.05）.However,the APA and APD50 as well as APD90 in right subepicardial myocytes were more significantly attenuated when comparing with left subepicardial myocytes after treated by lidocaine（P0.05 and 0.01,respectively）.With the voltage clamp protocol,lidocaine significantly decreased the INa under different command potential in subepicardial myocytes of left and right ventricular walls.And INa in right subepicardial myocytes was blocked more seriously than that in left subepicardial myocytes with administrating lidocaine.Under-20 mV voltage clamp,INa in left and right subepicardial myocytes were respectively decreased from（62.1±4.5） and（54.2±2.9） to（40.8±3.2）and（26.5±2.1） with lidocaine addition（compared with lidocaine group,P0.05 and 0.01,respectively）.Lidocaine shifted upward the I-V curves of INa of both left and right subepicardial myocytes,but lifted outstandingly the I-V curve of INa of right subepicardial myocytes on the top of all I-V curves.Moreover,lidocaine changed the peak potential of INa from-20 to-10 mV in left and right subepicardial myocytes.Conclusion： Lidocaine could completely elicited the cardiac electrical heterogeneity of left and right subepicardial myocytes in ventricular walls of rabbits,which attributed to AP and INa of right subepicardial myocytes which was attenuated more obviously than that of left subepicardial myocytes by administrating lidocaine.