选择性去心脏交感传入神经对犬急性心肌梗死后室性心律失常的影响

Effect of selective cardiac sympathetic afferent denervation on ventricular arrhythmias in an acute myocardial infarction canine model

目的探讨选择性去心脏交感传入神经(SCSAD)对犬急性心肌梗死(AMI)后自主神经功能、心室电生理特性和室性心律失常的影响。方法 24只成年雄性杂种犬随机分为对照组(n=8)、AMI组(n=8)和SCSAD组(n=8)。SCSAD组犬心外膜给予树胶脂毒素。对照组和AMI组犬心外膜涂抹不含树胶脂毒素的溶剂。AMI组与SCSAD组通过结扎冠状动脉(简称冠脉)左前降支建立AMI模型,对照组只分离穿线,不结扎冠脉。于结扎冠脉后15 min检测心率变异性(HRV),记录结扎后1 h室性心律失常的发生情况,对照组于相应时间点检测。ELISA法检测血清去甲肾上腺素(NE)水平。于结扎冠脉后1 h依次采用S_1S_2程控刺激测量心室有效不应期(ERP),S_1S_1 300 ms起搏测量单相动作电位(MAP)和S_1S_1动态起搏法测量动作电位时程(APD)电交替起搏周长。通过不同电压直接电刺激左侧星状神经节(LSG)后的最大收缩压变化百分比评价LSG功能。蛋白免疫印记法(Western blot)检测各组新鲜LSG组织的c-fos和神经生长因子(NGF)的表达。结果与对照组相比,AMI组HRV明显降低,SCSAD组较对照组和AMI组升高。相比对照组,AMI组和SCSAD组室性早搏发生增多,而SCSAD组较AMI组减少。与AMI组相比,SCSAD组室性心动过速发生减少,且SCSAD组与对照组相比无差异。与对照组相比,AMI组和SCSAD组血清NE水平升高,SCSAD组较AMI组低。与对照组相比,AMI组结扎后其缺血区心室ERP和MAP缩短,APD电交替起搏周长延长。SCSAD组较AMI组ERP和MAP延长,APD电交替起搏周长缩短,且SCSAD组较对照组ERP延长,MAP和APD电交替起搏周长无差异。AMI组LSG功能比对照组增强,SCSAD组较对照组和AMI组LSG功能减低。AMI组c-fos表达比对照组高,NGF表达二者无明显差异,而SCSAD组c-fos和NGF表达比AMI组低。结论 SCSAD降低AMI后心脏交感神经活性,提高心脏电生理稳定性,减少室性心律失常的发生。

Objective To investigate the effect of selective cardiac sympathetic afferent denervation(SCSAD) on autonomic nerve function, ventricular electrophysiological properties and the occurrence of ventricular arrhythmias after acute myocardial infarction(AMI) in dogs. Methods Twenty-four adult mongrel dogs were randomly divided into thecontrol group(n=8), AMI group(n=8) and SCSAD group(n=8). The dogs in SCSAD group received epicardial application of Resiniferatoxin. The vehicle was applied to the epicardium as a control. AMI was induced by left anterior descending coronary artery ligation. Heart rate variability(HRV) was detected at 15 minutes after AMI and at corresponding time points in the control group. AMI-induced ventricular arrhythmias were analyzed by continuous ECG recorded for 1 hour. Serum norepinephrin(NE) level was determined by enzyme-linked immunosorbent assay.Electrophysiological study was performed to examine ventricular effective refractory period(ERP)by programmed stimulation(S1 S2),monophasic action potentials(MAP)and the action potential duration(APD)alternates cycle length by dynamic steady-state pacing protocol(S1 S1).Left stellate ganglion(LSG) function was measured as the maximal change in systolic blood pressure in response to direct electrical stimulation of the LSG.Then,c-fos and nerve growth factor(NGF)protein expressed in the LSG were measured. Results Compared with the control group,AMI group significantly decreased HRV,whereas HRV of the SCSAD group was higher than that of control group and AMI group.The numbers of ventricular premature beat(VPB)episodes were significantly reduced in the SCSAD group compared with the AMI group.In addition,the episodes of ventricular tachycardia(VT)and the incidence of ventricular fibrilation(VF)were significantly lower,and mean duration of VT was significantly shorter in the SCSAD group than in the AMI group.Compared with the control group,the serum NE level in the AMI group and SCSAD group was elevated,and the serum NE level in the SCSAD group was lower than that in the AMI group.Compared with the control group,the ventricular ERP and MAP in ischemic area were shortened and the APD alternans cycle length was prolonged in the AMI group,while the ERP and MAP in the SCSAD group were prolonged and the APD alternans cycle length was shortened.The ERP of SCSAD group was longer than that of control group,and there was no significant difference in the MAP and the APD alternans cycle length.Compared with the control group,AMI group enhanced LSG function,whereas the increased LSG function was significantly attenuated in the SCSAD group.The expression of c-fos was higher in the AMI group than that in the control group,and there was no significant difference in the expression of NGF between the two groups,while the expression of c-fos and NGF in LSG in SCSAD group was lower than that in the AMI group. Conclusion SCSAD can reduce cardiac sympathetic nerve activity,improve cardiac electrophysiological stability,and reduce ventricular arrhythmias after AMI.