阻断神经元型Nav1.8通道对心脏交感神经节活性和心室电生理性质的影响

Effect of blocking neuronal Nav1.8 channel on the neural activity of cardiac sympathetic ganglion and ventricular electrophysiological parameters in normal canine

目的探讨阻断神经元型Nav1.8通道对正常犬心脏交感神经节活性和心室电生理性质的影响。方法16只健康成年犬(16~18kg)随机分为实验组(n=8)和对照组(n=8)。分离左侧心脏交感神经节,实验组向神经节内注射20mmol/L的Nav1.8通道特异性阻断剂(A-803467)0.1 ml,对照组向神经节内注射等体积的二甲基亚枫。在基础状态和药物注射60min后,分别记录左侧心脏交感神经节活性,并测定心室有效不应期(ERP)和动作电位时程(APD)。结果实验组在干预后心脏交感神经节的放电频率[(45±6)次/分vs(83±7)次/分,P<0.05]和幅度[(0.03±0.01)mV vs(0.05±0.01)mV,P<0.05]均显著降低,心室各部位ERP和APD_(90)显著延长,ERP离散度[(13±5)ms vs(21±4)ms,P<0.05]和APD_(90)离散度[(22±10)ms vs(38±14)ms,P<0.05]显著降低。而对照组以上指标无显著性改变(P>0.05)。结论阻断Nav1.8通道可显著降低心脏交感神经节活性,提高心室电生理稳定性。阻断Nav1.8通道可能具有抑制室性心律失常的作用。

Objective To investigate the effect of blocking neuronal Nav1.8 channel on the neural activity of cardiac sympathetic ganglion and ventricular electrophysiological parameters in normal canine. Methods Sixteen healthy canines（16-18 kg）were randomly divided into experimental group（n=8）and control group（n=8）.The left cardiac sympathetic ganglion was separated and 0.1 ml Nav1.8 channel specific blocker（A-803467）（20 mmol/L）was injected into the ganglion,while 0.1 ml dimethylsulfoxide was injected in control group.The neural activity of left cardiac sympathetic ganglion was recorded at baseline and 60 min after injection.In addition,the ventricular effective refractory period（ERP）and action potential duration（APD）were evaluated. Results In the experimental group,both the frequency[（45±6）impulses/min vs（83±7）impulses/min,P0.05）and amplitude[（0.03±0.01）mV vs（0.05±0.01）mV,P0.05]of the cardiac sympathetic ganglion activity were significantly decreased after blocking the Nav1.8 channel.In addition,the ventricular ERP and APD90 were significantly prolonged,and the dispersions of ERP [（13±5）ms vs（21±4）ms,P0.05]and APD90[（22±10）ms vs（38±14）ms,P0.05]were significantly decreased after injections in the experimental group.However,these parameters were not changed after injections in the control group（P0.05）. Conclusion Blocking the Nav1.8 channel could significantly inhibit the cardiac sympathetic ganglion activity and increase the stability of ventricular electrophysiology.Blocking the Nav1.8 channel in the cardiac sympathetic ganglion may prevent ventricular arrhythmia.