致心律失常性心肌病中心脏交感神经活性的研究  

Cardiac sympathetic nerve activity in arrhythmogenic cardiomyopathy

作　　者：周春江 张宝伟 吴奕章 张右铭 谢佳茜 杨兵[1] Zhou Chunjiang;Zhang Baowei;Wu Yizhang;Zhang Youming;Xie Jiaxi;Yang Bing(Shanghai Oriental Clinical College of Nanjing Medical University,Shanghai 200120,China;Department of Cardiovascular Medicine,The First Affiliated Hospital of Nanjing Medical University(Jiangsu Province Hospital),Nanjing 210029,China;Department of Cardiovascular Medicine,East Hospital Affiliated to Tongji University,Shanghai 200120,China)

机构地区：[1]南京医科大学上海东方临床医学院,上海200120 [2]南京医科大学第一附属医院(江苏省人民医院)心血管内科,南京210029 [3]同济大学附属东方医院心血管内科,上海200120

出　　处：《中华心律失常学杂志》2023年第3期258-264,共7页Chinese Journal of Cardiac Arrhythmias

基　　金：上海市浦东新区卫生系统重点专科建设(PWZzk2022-03);上海市浦东新区临床高峰学科项目(PWYgf2021-01)。

摘　　要：目的评估致心律失常性心肌病(ACM)患者交感神经功能,探究其与ACM恶性室性心律失常发生的关系及其机制。方法本研究为回顾性研究,选取2006年1月至2015年2月南京医科大学第一附属医院心内科确诊为ACM的患者(ACM组),同期纳入性别和年龄相匹配的健康对照者(HC组)。比较两组间心率变异性(HRV)相关指标,包括利用24 h动态心电图评估所有NN间期的标准差(SDNN)、平均NN间期的标准差(SDANN)、相邻NN间期差值的均方根(rMSSD)和差异>50 ms的NN间期的百分比(pNN50)。依据病程中是否发生持续性室性心动过速(sVT)将ACM组患者分为sVT亚组和非sVT亚组,比较两组间SDNN、SDANN、rMSSD和pNN50等交感神经活性指标。根据前期研究中发现的一个由DSG2-F531C突变引起的ACM家系,构建与该突变位点对应的DSG2-F536C纯合子突变小鼠作为ACM的研究模型(ACM小鼠),以野生型C57BL/6J小鼠(WT小鼠)作为对照,比较两组小鼠外周血中去甲肾上腺素(NE)的浓度及其心脏组织切片行免疫组织化学染色检测心脏交感神经分布情况。结果①ACM组69例患者,年龄(47.41±13.08)岁,其中男42例;HC组69例,年龄(46.32±14.26)岁,其中男42例。两组患者在年龄、性别、伴随疾病及吸烟等不良生活习惯方面差异无统计学意义(P>0.05)。②与HC组相比,ACM组患者SDNN水平显著降低[146.00(122.00,168.00) ms对120.00(92.50,137.50) ms,P<0.001],SDANN[134.00(109.00,147.00) ms对107.00(79.00,122.00) ms,P=0.001]、rMSSD[31.00(23.50,41.00) ms对28.00(24.50,37.50) ms,P=0.040]和pNN50[9.30(3.80,18.10)%对5.80(3.90,13.50)%,P=0.022]均明显降低,差异有统计学意义。③与非sVT亚组相比,sVT亚组患者SDNN[134.00(121.50,145.50) ms对104.50(87.00,129.50) ms,P<0.001]和SDANN[117.00(104.00,130.50) ms对90.5(70.50,114.50) ms,P<0.001]降低更为明显。④与WT小鼠相比,ACM小鼠外周血中的NE水平明显升高(P=0.015),心脏组织中酪氨酸羟化酶(TH)阳性交感神经纤维增加(P<0.Objective To evaluate sympathetic nerve function in patients with arrhythmogenic cardiomyopathy(ACM)and investigate the relationship between sympathetic nerve function and malignant ventricular arrhythmias(VA)in ACM and the mechanism within.Methods A retrospective study was analyzed on patients diagnosed with ACM in the Department of Cardiology,The First Affiliated Hospital of Nanjing Medical University,from January 2006 to February 2015(ACM group)and age-and gender-matched healthy controls(HC group).Sympathetic nerve activity was compared between the two groups using 24-hour ambulatory electrocardiogram to evaluate heart rate variability(HRV)related parameters,including standard deviation of all NN intervals(SDNN),standard deviation of average NN intervals(SDANN),square root of mean squared differences of successive NN intervals(rMSSD),and the percentage of NN intervals greater than 50 ms(pNN50).The ACM patients were further divided into(sustained ventricular tachycardia sVT)and non-sVT subgroups based on whether they experienced sVT during their history,and sympathetic nerve activity parameters were compared between the two subgroups.In addition,a mouse model of ACM harboring homozygous DSG2-F536C mutation,which was corresponding to the human pathogenic DSG2-F53IC mutation found in a previous study,and wild-type C57BL/6J mice(WT mice)were used to evaluate the concentration of norepinephrine(NE)in peripheral blood and the distribution of sympathetic nerves in cardiac tissue by ELISA and immunohistochemical staining,respectively.Results①Sixty-nine ACM patients and 69 healthy participants were enolled.The age[(47.41±13.08)vs.(46.32±14.26)years,P=0.640]and gender of male[42(60.87%)vs.42(60.87%),P=1.000]between ACM group and HC group were comparable.There was no significant difference between the two groups in terms of comorbidity,and unhealthty lifestyle such as smoking.②Compared with patients in the HC group,patients with ACM had significantly lower levels of SDNN[146.00(122.00,168.00)ms vs.120.00(92.50,137.

关 键 词：心动过速 室性 致心律失常性心肌病 心率变异性 交感神经重构 儿茶酚胺 

分 类 号：R541.7[医药卫生—心血管疾病]