The relationship between gap junctional remodeling and human atrial fibrillation

Atrial fibrillation (AF) is currently the most common cardiac tachyarrhythmia in clinical practice. AF has a tendency to become more persistent over time. Progression of an underlying disease is one explanation. Another possible explanation is electrical, structural, and gap junctional remodeling of the atrium by repetitive induction of AF. The expression level and distribution of it have close relation with the conduction velocity of electrical activation in the atrium. The aim of the present study was to investigate the alternations of the expression and distribution of ( connexin 40, Cx 40) and ( connexin 43, Cx 43) in the fight atrial appendages of the patients with AF by laser confocal scanning microscopy and Western blot technique.     

心肌细胞连接蛋白与心房颤动的关系

缝隙连接(gap junction,GJ)是含有多种细胞间通道的特殊膜结构,由连接蛋白(connexin,Cx)所构成,Cx40含量和分布的改变,可导致心房肌细胞电耦联传导速度改变,增加折返性心律失常,从而产生心房颤动(atrial fibrillation).本文对连接蛋白与心房颤动之间关系的研究进展作一综述.     

心房颤动与心房重构

心房颤动系临床上最常见的一种心律失常。心房重构是心房颤动发生和自我持续的核心环节,包括电重构、结构重构、组织重构、离子通道重构。     

心房肌间隙连接重构与风湿性瓣膜病患者心房颤动的关系

目的　探讨风湿性瓣膜病慢性心房颤动 (房颤 )患者心房肌组织中连接蛋白 4 0 (Cx4 0 )和连接蛋白 4 3(Cx4 3)蛋白质表达和分布的变化与慢性房颤的关系。方法　 32例风湿性心脏病患者 ,其中慢性房颤患者 2 1例 ,窦性心律者 11例 ,瓣膜置换术时取右心耳组织。用免疫荧光双标共聚焦显微镜和Western印迹观察Cx4 0和Cx4 3蛋白质表达和分布的改变。结果　激光共聚焦显微镜计算的Cx4 0荧光斑面积反映了蛋白表达水平 ,慢性房颤组为 0 6 7μm2 / μm3 ± 0 0 9μm2 / μm3 ,显著低于窦性心律组的 1 4 5 μm2 / μm3 ± 0 16 μm2 / μm3 (P <0 0 1) ,且细胞端端连接减少较侧侧连接处严重 ,分布呈现不均一性。Cx4 3总体表达水平未变 ,慢性房颤组为 1 38μm2 / μm3 ± 0 14 μm2 / μm3 ,窦性心律组为 1 5 3μm2 / μm3 ± 0 2 7μm2 / μm3 ,但侧侧分布增加而横向分布减少。Western印迹反映的Cx4 0和Cx4 3蛋白质表达水平与激光共聚焦观察结果一致。结论　心房肌Cx4 0和Cx4 3蛋白质水平降低和再分布可能与风湿性瓣膜病慢性房颤的发生和维持有关。     

心房颤动患者心房组织醛固酮水平与心房结构重构的相关性研究

目的:探讨心房颤动患者心房组织醛固酮水平和心房结构重构的相关性.方法:入选进行人工心脏瓣膜置换术的风湿性心脏病患者25例,其中窦性心律者12例,慢性心房颤动者13例(房颤时间≥6个月).上述患者均于手术时取左右心房侧壁组织(窦性心律:右房标本＝12,左房标本＝7;房颤心律:右房标本＝13,左房标本＝8),用放射免疫法测定心房组织醛固酮水平;用免疫组织化学法对Ⅰ型胶原和Ⅲ型胶原容量分数(CVF-Ⅰ,CVF-Ⅲ)进行半定量分析;用VG染色法对总胶原容量分数(CVF)进行半定量分析.结果:与窦性心律组比较,心房颤动组左房内径显著扩大(P＜0.01 ); 心房肌组织醛固酮、CVF-Ⅰ、CVF-Ⅰ/CVF-Ⅲ比值及CVF均明显增加(P＜0.01);两组CVF-Ⅲ无差异;上述指标在左右心房之间无差异;CVF-Ⅰ与左心房直径(r=0.856,P＜0.001)、CVF-Ⅰ/CVF-Ⅲ比值与心房颤动时间(r=0.766,P＜0.01)、CVF与左心房直径(r=0.845,P＜0.001)均显著正相关;心房组织醛固酮水平与左心房内径(r=0.814,P＜0.001)和CVF(r=0.885,P＜0.001)呈明显正相关.结论:心房组织醛固酮水平在心房颤动心房结构重构中起重要作用,并可能参与了心房颤动的发生和维持.     

Electrical remodeling in human atrial fibrillation

Atrial fibrillation is the most common clinically important cardiac arrhythmia accounting for 20％ to 25％ of strokes and is a common cause of congestive heart failure.1,2 With the aging population and changing demographics,atrial fibrillation has become an epidemic affecting 2.66 million people in the United States.The prevalence of atrial fibrillation is estimated to increase by 5 fold to 12 million by 2050.3 The diagnosis and treatment of atrial fibrillation represent a significant health care burden of $15.7 billion per year.4 Treatment of atrial fibrillation using antiarrhythmic drugs has been disappointing,while radiofrequency ablation approaches have limitations,including unclear long-term efficacy.Innovation in treatment is needed and pursuit of novel modalities of therapy requires fundamental knowledge in the molecular mechanisms that lead to atrial fibrillation,including electrical remodeling in atrial fibrillation.     

心房颤动电生理重构的实验研究

目的 :研究心房颤动 (atrialfibrillation ,AF)时心房肌的电生理重构。方法 :快速持续起搏犬右心房 8～ 10周 ,制备持续性AF模型。比较对照犬 ( 8只 )与起搏犬 ( 10只 )的有效不应期 (effectiverefractoryperiod ,ERP)和心房颤动波周长 (atrialfibrillationcyclelength ,AFCL)的变化来分析心房肌的电生理重构。结果 :起搏组P波时间和PA间期比起搏前明显延长 (P波时间 90 5± 10 5对 5 3 6± 8 3ms ;PA间期 5 9 6± 8 8对 3 8 6± 11 4ms ,P <0 0 5 )。经程序刺激ERP较对照组明显缩短 (S1S13 0 0ms 115± 2 3对 15 0± 2 1;S1S14 0 0ms 10 5± 2 7对 15 4± 2 4ms ,P <0 0 5 )。同一心房不同部位的ERP和AFCL也存在差异。结论 :心房率的长期变化可引起ERP和AFCL的变化 ,即心房肌发生电生理重构 ,而且不同部位心房肌电生理重构是不同的。     

Changes in microRNAs expression are involved in age-related atrial structural remodeling and atrial fibrillation

Background Small noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of extracellular matrix proteins.However,their role in age-related cardiac remodeling and atrial fibrillation (AF) was not well understood.The present study was designed to decipher molecular mechanisms underlying age-related atrial structural remodeling and AF.Methods Three groups of dogs were studied:adult and aged dogs in sinus rhythm and with persistent AF induced by rapid atrial pacing.The expressions of microRNAs were measured by quantitative real-time polymerase chain reaction.Pathohistological and ultrastructural changes were tested by light and electron microscopy.Apoptosis index of myocytes was detected by TUNEL.Results Samples of atrial tissue showed the abnormal pathohistological and ultrastructural changes,the accelerated fibrosis,and apoptosis with aging and/or in AF dogs.Compared to the adult group,the expressions of microRNAs-21 and -29 were significantly increased,whereas the expressions of microRNAs-1 and-133 showed obvious downregulation tendency in the aged group.Compared to the aged group,the expressions of microRNAs-1,-21,and-29 was significantly increased in the old group in AF; contrastingly,the expressions of microRNA-133 showed obvious downregulation tendency.Conclusion These multiple aberrantly expressed microRNAs may be responsible for modulating the transition from adaptation to pathological atrial remodeling with aging and/or in AF.     

Effects of trimetazidine on atrial structural remodeling and platelet activation in dogs with atrial fibrillation

Atrial fibrillation （AF） is one of the most common .arrhythmias in clinical practice. AF results in electrophysiological alterations which involve increased atrial effective refractory period and atrial effective refractory period dispersion, reduced rate adaptation of atrial effective refractory period, and slowed atrial conduction. These variances promote their own maintenance-AF begets AF.1 Previous study suggested that Ca^2＋ overload and metabolic derangement contributed to electrophysiological remodeling in AF. However, we did not demonstrate a persistent disturbance in energy metabolism during AF in our previous study,     

迷走神经张力与碎裂电位及房颤之间的关系研究

目的研究迷走神经张力与碎裂电位及房颤之间的关系研究。方法健康成年杂种犬15只随机分为3组,A组心外膜脂肪垫注射氯化乙酰胆碱（Ach）1mg;B组心外膜脂肪垫注射氯化乙酰胆碱5mg;C组心外膜脂肪垫注射生理盐水共5ml。3组均于注射后行BURST刺激记录房颤诱发与否,房颤诱发时间,左房侧壁（A点）、左房后壁（B点）、左心耳（C点）碎裂电位持续时间。结果 C组房颤诱发率于注射生理盐水前后予BURST刺激无明显变化。A、B组乙酰胆碱注射后房颤诱发率显著增加,但A、B两组房颤诱发率无显著变化。C组房颤持续时间较A组[C vs A：（7.00±2.10）svs（50.42±6.36）s,P=0.013;C vs B：（7.00±2.10）s vs（143.24±11.28）s,P〈0.001]短。B组房颤持续时间长于A组[（143.24±11.28）s vs（50.42±6.36）s,P〈0.001]。C组左房侧壁,后壁位点碎裂电位持续时间均较A、B组相应位点短。[C,A,B组：A点（2.2±0.5）s vs（37.4±6.3）s vs（132.5±12.7）s,P〈0.0001];[B点（2.2±0.5）s vs（37.2±6.3）svs（132.5±12.7）s,P〈0.001];C组左心耳（C点未能记录到碎裂电位）。A组碎裂电位持续时间较B组短[A点：（37.4±6.3）s vs（132.5±12.7）s,P〈0.001;B点：（37.2±6.3）s vs（132.5±12.7）s,P〈0.0001;C点：（35.1±6.7）s vs（130.7±13.3）s,P〈0.0001]。A,B组自身对照,左心耳位点较左房侧壁、后壁碎裂电位持续时间短[A组：（37.4±6.2）svs（37.2±6.3）s vs（35.1±6.7）s,P〈0.0001;B组：（132.4±12.7）s vs（132.5±12.7）s vs（130.7±13.3）s,P〈0.0001]。C组左房侧壁,后壁碎裂电位时间差异无统计学意义（2.25±0.5）s vs（2.25±0.5）s,P=0.183]。结论迷走神经张力越高,越容易产生碎裂电位,则房颤持续时间愈长。     

心房颤动患者CA-125表达水平及其意义

目的：探讨CA-125在阵发性和持续性心房颤动（简称房颤）患者中的表达水平及其意义。方法：回顾性分析2017年6月至2018年6月在温州医科大学附属第一医院住院的642例房颤患者临床资料。将入组房颤患者根据阵发/持续房颤分为2组,比较临床资料（年龄、性别、BMI、房颤病程、左房内径、射血分数、BNP、肝肾功能、CHA2DS2-VASc评分、CA-125等）,应用多因素logistic回归分析持续性房颤的危险因素。结果：与阵发性房颤患者相比,持续性房颤患者的CA-125水平更高（P＜0.001）。Logistic回归分析显示CA-125是持续性房颤的独立危险因素（P＜0.05）。结论：CA-125可能是持续性房颤的预测指标。     

Calpain I inhibition prevents atrial structural remodeling in a canine model with atrial fibrillation

Background Atrial fibrillation （AF） is accompanied by atrial structural remodeling. Calpain activity is induced during AE To test a causal relationship between calpain activation and atrial structural changes, N-acetyI-Leu-Leu-Met （ALLM）, a calpain inhibitor, was utilized in a canine AF model. Methods Fifteen dogs were randomly divided into 3 groups： sham-operated group, control group and calpain inhibitor group; each with 5 dogs. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute for 3 weeks. ALLM was administered at a dosage of 1.0 mg-kg-l-d1 in the calpain inhibitor group. Three weeks later, the proteolysis, protein expression of TnT and myosin, calpain I localization and expression and structural changes were examined in left atrial free walls, right atrial free walls and the interatrial septum respectively. Atrial size and contractile function were also measured by echocardiography. Results Long-term rapid atrial pacing induced marked structural changes such as enlarged atrial volume, myolysis, degradation of TnT and myosin, accumulation of glycogen and changes in mitochondrial shape and size, which were paralleled by an increase in calpain activity. The positive correlation between calpain activity and the degree of myolysis （rs=0.90 961, P〈0.0001） was demonstrated. In addition to structural abnormalities, pacing-induced atrial contractile dysfunction was observed in this study. The pacing-induced atrial structural alterations and loss of contractility were partially prevented by the calpain inhibitor ALLM. Conclusions Activation of calpain represents key features in the progression towards overt structural remodeling. Calpain inhibitor, ALLM, suppressed the increased calpain activity and reversed structural remodeling caused by sustained atrial fibrillation in the present model. Calpain inhibition may therefore provide a possibility for therapeutic intervention in AE     

心外膜脂肪组织及其在房颤心肌结构重构和电重构中的作用

心房纤颤（atrial fibrillation, AF）是临床上最常见的心律失常之一,也是心血管疾病发病率和死亡率增加的重要原因。心外膜脂肪（epicardial adipose tissue, EAT）是位于脏层心包和心肌之间的一种特殊脂肪组织,研究表明EAT参与AF的发生与维持,但是具体机制尚未得到完全阐释。EAT来源的脂肪干细胞（adipose-derived stromal cells, ADSCs）分泌的细胞外囊泡(extracellular vesicles, EVs) 近年来受到重视。该文主要从EAT特点、定量检测及其与心肌结构与电重构的关系,特别是EVs对AF发生的影响等方面进行综述,以期进一步认识AF的发病机制,为今后的治疗提供新的思路。     

射频消融术对心肌病阵发性心房颤动患者心脏逆重构的影响

目的：探讨导管射频消融术( RFCA )对心肌病阵发性心房颤动( PAF)患者心脏结构逆重构及生活质量的影响。方法62例PAF患者[左室舒张末径( LVEDD)男≥55 mm,女≥50 mm]均行环肺静脉隔离术为RFCA组。同期住院的相匹配的33例患者进行药物频率控制治疗(静息时心室率控制在60~80次/min,活动时<100次/min)为药物治疗组。入院72 h及心率达标时,术后6个月或频率控制6个月后分别行SF-36量表对患者进行生活质量评分,窦性心律下行经胸心脏彩超检查,测量患者的左房内径( LAD )、LVEDD、左室射血分数( LVEF)。结果 RFCA组患者术后第6个月LVEDD、LAD均较术前减小, LVEF增加差异有统计学意义(P<0．05)。药物治疗组患者LVEDD、LAD均较术前增加(P<0．05),LVEF变化不大。心理健康、躯体疼痛和总健康状况差异无统计学意义。 RFCA组和药物治疗组于社会功能、躯体功能、情感角色、躯体角色和精力有明显改善( P<0．05), RFCA组改善更明显( P<0．05)。结论心肌病PAF患者行RFCA术后维持窦性心律可以逆转患者的心脏重构,生活质量得到明显改善。     

氧化应激标志物在房颤患者心房结构重构中的变化及意义

目的通过分析多种氧化应激标志物在血清及组织中的动态变化,观察其在心房结构重构中的表达,探讨房颤(atrial fibrillation,AF)的发生机制。方法选择我中心44例2014年2-5月行单纯二尖瓣置换手术的风湿性心脏病患者,根据病史及术前动态心电图记录分为2组:持续性房颤(AF)组26例,窦性心律(SR)组18例。术中取部分右心耳组织,行Masson染色观察纤维化情况,采用免疫组化、免疫荧光染色法观察右心耳组织NOX2蛋白表达,用ELISA法测定右心耳组织中丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、活性氧(reactive oxygen species,ROS)、晚期氧化蛋白产物(advanced oxidative protein products,AOPP)浓度以及血清中ROS、AOPP含量。结果 AF组心房组织中MDA[(15.41±1.69)μmol/mg]、SOD[(13.32±1.25)μmol/mg]、ROS[(18.53±3.47)μmol/mg]、AOPP[(29.69±2.09)μmol/mg]含量与SR组MDA[(11.46±1.83)μmol/mg]、SOD[(10.65±1.15)μmol/mg]、ROS[(13.65±3.29)μmol/mg]、AOPP[(21.94±1.94)μmol/mg]比较差异有统计学意义(P<0.05),AF组血清中ROS含量[(34.6±2.61)μmol/L]明显高于SR组[(17.8±1.03)μmol/L],2组患者血清中AOPP含量差异无统计学意义(P>0.05)。与SR组相比,AF组右心耳组织胶原纤维增生明显,NOX2蛋白表达呈强阳性。结论房颤时发生以间质纤维化改变的心房结构重构,氧化应激参与了房颤发生和结构重构过程。     

缬沙坦对风湿性心脏病心房颤动患者心房重构的影响

目的探讨缬沙坦对风湿性心脏病心房颤动患者心房重构的影响。方法 50例风湿性心脏病二尖瓣病变合并心房颤动患者分为缬沙坦组27例和对照组23例,对照组给予利尿剂、洋地黄制剂、β受体阻滞剂等常规治疗,缬沙坦组在常规治疗的基础上加用缬沙坦治疗。应用超声心动图测定左心房内径和容积,记录二尖瓣血流频谱A峰流速(VA)和左心房射血力(LAEF)。行心脏外科手术时取右心耳组织,并应用V-G染色法和VIDAS-21图像分析系统测量心房组织胶原容积分数(CVF)。结果治疗后缬沙坦组左心房前后径、最大容积、最小容积、心房CVF明显低于对照组,VA、LAEF明显高于对照组,差别均有统计学意义(P<0.05)。结论缬沙坦可明显降低风湿性心脏病心房颤动患者左心房重构程度,从而阻止心房颤动的发生发展。     

频发房性早搏与新发心房颤动及不良预后的关系

目的 评估频发房性早搏（permature atrial complexes,PACs）与新发心房颤动（new-onset atrial fibrillation,NAF）及不良预后的关系。方法 连续入选因心悸、眩晕或晕厥入院的患者,收集患者基线资料,记录18个月内的NAF及不良事件（缺血性卒中、充血性心力衰竭及死亡）。结果 根据患者Holter检查记录的PACs次数将患者分为2组,频发PACs组患者年龄较高,左房较大,射血分数较低。18个月后,频发PACs组患者NAF（29.2%vs9.0%,P〈0.05）及不良事件（34.4%vs19.4%,P〈0.05）发生率高于无频发PACs组患者。Cox回归分析也显示,频发PACs是NAF及不良事件的独立危险因素（P〈0.05）。结论 频发PACs可预测患者的AF发生及不良预后。     

小电导钙激活钾通道促房颤自稳的机制研究进展

心房颤动(房颤)是临床常见的心律失常,房颤易自发由阵发性向持续性乃至永久性发展,即房颤自稳现象,而心房电重构是房颤自稳过程中具有代表性的心房电生理改变.小电导钙激活钾通道(small conductance Ca2+-activated K+ channels,SK通道)是近年发现的广泛分布于心肌细胞中的离子通道,具有对胞内钙离子高敏感性的特点.SK通道在心房肌细胞的电重构中具有重要作用,尤其在促进房颤自稳并致使房颤持久化的机制中扮演了重要角色.本文旨在通过综述近年相关研究,总结SK通道促房颤自稳性的机制及相应的干预措施,并结合临床实际进行讨论.     

心房颤动与心房肌缝隙连接蛋白变化的关系研究

目的　探讨心房肌缝隙连接 (GJ)蛋白变化与心房颤动 (房颤 )间的关系。方法　收集风湿性瓣膜病患者 2 7例 ,先心病对照 3例 ,分对照、无房颤 (NAF)、阵发性房颤 (PAF)和持续房颤 (AF)组 ,术中取右心耳组织 ,采用Westernblot方法在纤维膜上显示Cx43和Cx40特异性条带 ,分析条带显色强度判断Cx含量 ,进行组间t检验。结果　Cx43在NAF组和AF组间差异无统计学意义 (P =0 76)。Cx40在膜上的显色比Cx43浅 ,在NAF组和AF组间显示出差异有统计学意义 (P =0 0 0 1 ) ,在PAF组显示出升高趋势。Cx40在左房径 >5 0mm者与左房径≤ 5 0mm患者相比无显著性差异 (P >0 0 5 )。结论　Cx40在房颤患者中减低 ,其重构参与房颤的产生和维持     

微纤维蛋白1在瓣膜性心房颤动患者心房组织中的表达及其与心房纤维化的关系

目的：观察微纤维蛋白1（FBN-1）在风湿性心脏瓣膜病并发心房颤动（AF）患者心房组织中的表达,探讨FBN-1与心房纤维化的关系。方法：选择因风湿性心脏瓣膜病住院并行瓣膜置换手术的患者84例,分为AF组39例和窦性心律（SR）组45例;收集整理患者的临床资料,并于手术中获取右心房组织（0.3~0.5 mm³）。Masson 染色观察2组患者右心房纤维化程度;Western blotting法测定各组患者心房组织中FBN-1蛋白的表达,相关分析探讨FBN-1与心房纤维化的关系。结果：2组患者在性别构成比、年龄、血压、血常规和生化指标等方面比较差异无统计学意义（P>0.05）。AF组患者左和右心房直径明显大于SR组（P<0.05）;Masson 染色,AF组患者心房组织存在明显纤维化,AF组患者胶原容积分数和胶原水平明显高于SR组（P<0.05）;AF组患者心房组织中FBN-1的蛋白表达水平明显高于SR组（P<0.05）;瓣膜性AF患者右心房组织FBN-1蛋白表达水平与胶原水平呈正相关关系（r=0.544,P=0.021）。结论：瓣膜性AF患者心房组织存在明显的心房纤维化,与FBN-1基因转录水平上调有关联。