心房肌钙激活中性蛋白酶基因转录表达改变与心房颤动的关系

目的研究风湿性心脏瓣膜病（风心病）心房颤动（房颤）患者心房肌细胞钙激活中性蛋白酶（calpain1、calpain2）、钙激活中性蛋白酶（calpastatin）及L-型电压依赖钙通道alc亚基（LVDCCalc）的基因转录，探讨房颤患者心房肌电重构和结构重构以及心功能下降的分子生物学机制及其在房颤发生维持中的作用。方法采集风心病窦性心律组患者12例和房颤组患者16例的右心耳组织，应用半定量逆转录-聚合酶链反应（RT-PCR）方法，测定心房肌calpain1、calpain2、calpastatin及LVDCCalc的mRNA表达水平。应用电镜观察房颤组与窦性心律组心房肌细胞超微结构。结果与窦性心律组相比，房颤组心房肌calpain1的mRNA表达水平上调（P〈0．05），LVDCCalc的mRNA表达水平显著下调（P〈0．01），且与calpainl的mRNA表达呈负相关（r=-0．583，P=0．019），而calpain2和calpastatin的mRNA表达水平差异无统计学意义（P〉0．05）；电镜结果显示房颤组心房肌细胞超微结构发生明显变化。结论房颤患者心房肌细胞calpain1和LVDCCalc的转录水平调控失衡，提示calpain1激活影响心肌细胞结构和通道蛋白水平，与房颤心房电重构和结构重构有关。     

慢性心房颤动患者心房肌钙转运调控蛋白和钙激活中性蛋白酶基因转录表达的变化

目的探讨心房颤动(简称房颤)患者心房肌电和结构重构以及心功能下降的分子生物学机制。方法采集风湿性心脏瓣膜病(简称风心病)窦性心律患者12例(窦律组)和房颤患者16例(房颤组)的右心耳组织,应用半定量逆转录-聚合酶链反应方法,测定心房肌钙转运调控蛋白和钙激活中性蛋白酶(calpain1)的mRNA表达水平。结果与窦律组比较,房颤组L-型电压依赖钙通道a1c亚基(LVDCCa1c)、肌浆网Ca2+-ATP酶、兰尼碱受体的mRNA表达水平显著下调(P均<0.01),三磷酸肌醇受体的mRNA表达水平上调(P<0.05);房颤组心房肌cal-pain1的mRNA表达水平上调(P<0.05),且与LVDCCa1c的mRNA表达呈负相关(r=-0.583,P=0.019)。结论房颤患者心房肌钙转运调控蛋白和calpain1转录水平调控失衡可能是心房肌电和结构重构以及心功能下降的分2子生物学机制之一。     

心房肌钙转运调控蛋白的表达改变与增龄及心房颤动关系的实验研究

目的:为论证是否存在心房肌细胞膜L-型钙通道蛋白和细胞内肌质网钙转运调控蛋白异常表达伴随增龄而显现,致使心肌细胞内钙稳态遭到破坏,以期阐明增龄性心房颤动(房颤)心房电重构的分子机制。方法:通过持续快速心房起搏建立慢性房颤犬模型,用实时荧光定量聚合酶反应(QRT-PCR)和蛋白免疫印迹(Western blot)方法检测4组犬(成年和老年窦性心律犬、成年和老年慢性房颤犬)左心房心肌钙转运调控蛋白在mRNA和蛋白质表达水平的变化。结果:窦性心律时,与成年犬比较,老年犬心电图P波持续时间显著延长,P波离散度显著增大,在mRNA和蛋白质表达水平方面,窦性心律时,与成年犬比较,老年犬左心房肌L-钙通道a1c亚基(LVDCCa1c)显著降低,而Ca2+-ATPase显著升高(P0.05),RYR2、IP3R1和PLN普遍显示出上调趋势,但无统计学差异(P0.05);与窦性心律犬比较,相同年龄组房颤犬除受磷蛋白(PLN)之外,LVDCCa1c和肌浆网钙转运调控蛋白均显著下调,尤其是老年房颤犬这种下调趋势更加明显(P0.05)。结论:伴随增龄与房颤而显现的左房电生理和钙转运调控蛋白特异性改变可能是增龄性房颤心房电重构的分子机制。     

西拉普利和缬沙坦与心房颤动犬心房肌钙激活蛋白酶表达及心房结构重构关系的实验研究

目的 观察西拉普利和缬沙坦对心房颤动(房颤)犬心房肌钙激活蛋白酶(calpairIs)mR-NA和蛋白表达及心房结构重构的影响.方法 27只犬随机分为假手术组、对照组、西拉普利组和缬沙坦组.对照组、西拉普利组和缬沙坦组犬以400次/min心房快速起搏6周,建立房颤犬模型.假手术组犬埋植起搏器后不起搏.测量左心房容积及收缩功能变化,记录房颤诱发及维持情况,检测心房肌calpains mRNA和蛋白表达,观察心房肌病理组织学和超微结构改变.结果 西拉普利组和缬沙坦组犬心房肌calpain I mRNA和蛋白表达较假手术组增多(P＜0.05),但较对照组显著减少(P＜0.01).各组犬心房肌calpain I蛋白表达与肌溶解高度相关(r=0.89,P＜0.01).各组犬心房肌calpainⅡmRNA和蛋白表达差异无统计学意义.与对照组相比,西拉普利组和缬沙坦组犬心房肌病理组织学和超微结构改变显著减轻,左心房及左心耳容积明显减小,左心房收缩功能显著增强,房颤诱发率和持续时间明显降低.结论 房颤犬心房肌calpain I mRNA和蛋白表达显著上调.西拉普利和缬沙坦能明显抑制房颤犬心房肌ealpain I表达,防治心房结构重构,减少房颤发生.     

风湿性心脏病慢性心房颤动患者钙转运调控蛋白和钙激活中性蛋白酶基因转录的表达改变

目的测定心房肌钙转运调控蛋白和钙激活中性蛋白酶(calpain1)的mRNA表达,探讨风湿性心脏瓣膜病(风心病)心房颤动(房颤)患者心房肌电重构和结构重构以及心功能下降的分子生物学机制及其在房颤发生、维持中的作用。方法采集风心病窦性心律组患者12例和房颤组患者16例的右心耳组织,应用半定量逆转录-聚合酶链反应(RT-PCR)方法,测定心房肌钙转运调控蛋白和calpain1的mRNA表达水平。结果与窦性心律组相比,房颤组L-型电压依赖钙通道a1c亚基(LVDCCa1c)、肌浆网Ca2+-ATP酶、兰尼碱受体(RYR2)的mRNA表达水平明显下调(均为P<0.01),三磷酸肌醇受体(IP3R1)的mRNA表达水平上调(P<0.05),房颤组心房肌calpain1的mRNA表达水平上调(P<0.05),且与LVDCCa1c的mRNA表达呈负相关(r=-0.583,P<0.05)。结论房颤患者心房肌钙转运调控蛋白和calpain1转录水平调控失衡可能是心房肌电重构和结构重构以及心功能下降的分子生物学机制之一,与房颤的发生和维持有关。     

心房颤动患者心房细胞结构的改变

目的探讨心房颤动(房颤)发生后相关细胞结构和超微结构变化及其临床意义。方法收集53例心脏外科手术患者,根据心律分为窦性心律组(窦律组,26例)和房颤组(27例)。术前行超声心动图检查。手术中取右心耳组织,行石蜡包埋切片,HE染色后测定细胞直径,Masson染色测定胶原容积分数。用免疫组织化学方法检测结蛋白、N-钙黏素的分布变化。电镜观察超微结构变化。结果与窦律组比较,房颤组心房细胞直径增加,与心房大小成正相关,心房纤维化明显,心肌出现不同程度的肌溶解现象,电镜观察发现细胞器、细胞连接异常。免疫组织化学检测显示房颤组中N-钙黏素分布不均一,结蛋白分布异常。结论房颤后心房细胞结构改变是房颤复发和心房抑顿的结构基础。     

氧化应激对心房颤动犬心房肌细胞凋亡及凋亡相关蛋白影响的研究

目的 观察普罗布考(probucol)对长期心房快速起搏诱发心房颤动(房颤)犬心房肌细胞凋亡及凋亡相关蛋白表达的影响,探讨氧化应激在房颤心房结构重构中的作用.方法 杂种犬20只,随机分为假手术组(n=6)、对照组(n=7)和普罗布考组(n=7).无菌条件下开胸后在犬右心房缝植4对心外膜记录电极,电极尾端经皮下由犬背部穿出;在右心耳缝植螺旋型起搏电极,连接实验用AOO高频起搏器(400次/min),心房快速起搏6周,建立房颤犬模型;假手术组犬仅缝植心外膜记录电极和起搏电极但不起搏;对照组及普罗布考组犬心房快速起搏6周;普罗布考组于起搏前一周开始服用普罗布考(100 mg·kg-1·d-1),直至起搏结束.TUNEL法检测心房肌细胞凋亡情况;免疫组化方法及免疫印记法检测凋亡相关蛋白caspase-3、bcl-2和bax表达情况;免疫组化方法检测calpain Ⅰ表达;比色法检测心房肌总抗氧化能力(T-AOC)、丙二醛(MDA)和抗超氧阴离子(抗O2-)水平;于起搏前、起博6周后,经心外膜电极记录各组犬房颤诱发情况.结果 与假手术组犬相比,对照组犬左、右心房肌凋亡细胞数量显著增加[(44.3±9.7)% vs (1.36±0.70)%,(42.1±11.9)% vs (1.07±0.50)%,P＜0.01],心房肌caspase-3、bax和calpain Ⅰ表达明显上调(P＜0.01),bcl-2表达显著下调(P＜0.01).与对照组犬相比,普罗布考组犬左、右心房肌凋亡细胞数量明显减少[(21.4±5.8)% vs (44.3±9.7)%,(20.1±6.1)% vs (42.1±11.9)%,P＜0.01],calpain Ⅰ、caspase-3和bax表达显著下调(P＜0.01),bcl-2表达增加(P＜0.05).与假手术组犬相比对照组犬心房肌MDA水平明显增加(P＜0.01),T-AOC、抗O2-水平明显降低(P＜0.01);与对照组犬相比,普罗布考组犬心房肌MDA水平显著降低(P＜0.05),T-AOC、抗O2-水平显著增加(P＜0.01).对照组和普罗布考组起搏后房颤诱发率和平均持续时间均较起搏前显著增加(P＜0.05);起搏后普罗布考组房颤诱发率较对照组降低(P＜0.05),房颤平均持续时间显著减少(P＜0.01).结论 普罗布考可能通过抑制氧化应激,增加bcl-2表达,降低calpain Ⅰ、caspase-3和bax表达,阻止长期心房快速起搏诱发房颤犬心房肌细胞凋亡,对房颤心房结构重构防治有益,能够减少房颤发生.     

心房颤动患者L型钙通道电流改变的分子基础

目的　研究心房颤动 (房颤 )患者L型钙通道电流 (ICa L)重塑的分子基础。方法　以窦性心律患者 (窦律组 )为对照 ,应用RT PCR、免疫组化和免疫电镜方法检测阵发性房颤、≤ 6个月和>6个月的慢性房颤患者心房肌L型电压依赖钙通道 (LVDCC)α1c亚基 (α1c)基因和蛋白表达 ,用图像分析系统对组化抗原表达进行半定量分析。结果　与窦律组比较 ,LVDCCα1cmRNA和蛋白表达在 >6个月慢性房颤组中显著下降 ,在阵发性房颤组中无明显改变 ,在≤ 6个月慢性房颤组中其蛋白表达明显下降 ,而mRNA表达无明显改变。结论　慢性房颤伴发LVDCCα1c蛋白表达下调 ,提示心房肌细胞LVDCC密度下调 ,可能是其ICa L下降的分子基础。     

血管紧张素Ⅱ受体拮抗剂对心肌重构的保护机制

目的:探讨血管紧张素Ⅱ(AngⅡ)受体(AT1,AT2)拮抗剂对梗死心肌组织中钙蛋白酶(calpain)系统的作用。方法:结扎大鼠左冠状动脉建立心肌梗死(MI)模型,将成功造模的96只大鼠分为4组,每组24只。各组术后1、3、7、14d分别检测左心室游离壁(LVFW)、室间隔(IS)、右室壁(RV)的calpainⅠ、Ⅱ及钙蛋白酶抑制蛋白(calpastatin)表达。结果:术后14d,手术组IS的calpainⅠ蛋白表达与LVFW的calpainⅡ蛋白表达均明显高于假手术组、手术加缬沙坦组及手术加PD123319组(均P<0·01);各组LVFW、RV的calpainⅠ蛋白表达,IS、RV的calpainⅡ蛋白表达以及IS、LVFW、RV的calpastatin蛋白表达差异均无统计学意义。结论:calpainⅠ参与MI的晚期重塑,calpainⅡ参与早期缺血心肌组织的损伤作用。MI病理过程中,calpainⅠ和Ⅱ的上调通过AT1起作用,AT1受体拮抗剂的心脏保护作用与其抑制了calpain系统有关。     

风湿性心脏病心房颤动患者心房肌超微结构改变的研究

探讨风湿性心脏病(简称风心病)心房颤动(简称房颤)患者心房肌超微结构改变与房颤维持的相关关系。选取进行人工瓣膜置换术的风心病房颤患者24例为房颤组,风心病窦性心律(简称窦律)患者12例为窦律组。上述患者于手术时取左心耳心肌标本,进行电镜的定性研究。结果:与窦律组相比,房颤组心房肌的超微结构特点有:心肌细胞肌原纤维溶解、断裂,线粒体占据了肌原纤维的位置;在肌原纤维溶解区糖原积聚,形成“糖原湖”;线粒体数量明显增多,且大小不一;细胞核异型明显;闰盘扭曲,盘旋重叠,模糊、不连续;心肌间质纤维增生明显。结论:风心病房颤组患者心房肌超微结构改变可能是导致风心病患者房颤持续的重要病理基础。     

Treatment of atrial flutter and rapid atrial tachycardia with transesophageal atrial pacing

Eight patients with atrial flutter (AF) and rapid atrial tachycardia (AT) (5 common AF, 1 uncommon AF and 2 AT) were treated with transesophageal atrial pacing (TEAP). In 5 patients no antiarrhythmic agent was used during this study, and in 3 patients procainamide was administrated intravenously. Conversion to sinus rhythm was successfully achieved in 7 patients (5 common AF and 2 AT). Two patients were converted to sinus rhythm immediately after pacing, and transient atrial fibrillation was induced before conversion to sinus rhythm in 5 patients. TEAP failed to terminate the arrhythmia in 1 patient with uncommon AF. Administration of procainamide reduced the atrial rate in 2 common AF and 1 AT, which were successfully converted to sinus rhythm by TEAP, but induced a rapid ventricular response in 2 patients, one of whom also developed hypotension before conversion. No significant complication due to TEAP was observed in this study. In conclusion, TEAP is a noninvasive method with fewer complications and has nearly the same high efficacy for converting AF and rapid AT to sinus rhythm as DC cardioversion or transvenous atrial pacing.     

Simultaneous occurrence of atrial fibrillation and atrial flutter

INTRODUCTION: Early reports suggested that some patients with "atrial fibrillation/flutter" might have atrial fibrillation in one atrium and atrial flutter in the other. However, more recent conceptions of atrial fibrillation/flutter postulate that the pattern is due to a relatively organized (type I) form of atrial fibrillation. We report the occurrence and ECG manifestations of simultaneous atrial fibrillation and flutter in patients undergoing attempted catheter ablation of atrial flutter. METHODS AND RESULTS: In patients undergoing radiofrequency ablation for atrial flutter, an attempt was made to entrain atrial flutter by pacing in the right atrium. The arrhythmias observed occurred following attempts at entrainment, or spontaneously in one case. Twelve transient episodes of simultaneous atrial fibrillation and flutter were observed in five patients. The atrial fibrillation was localized to all or a portion of one atrium, during which the other atrium maintained atrial flutter. In each case, the surface 12-lead ECG reflected the right atrial activation pattern. No patients had interatrial or intra-atrial conduction block during sinus rhythm, suggesting functional intra-atrial block as a mechanism for simultaneous atrial fibrillation/flutter. CONCLUSION: In certain patients, the occurrence of transient, simultaneous atrial fibrillation and flutter is possible. In contrast to prior studies in which it was suggested that left atrial or septal activation determines P wave morphology, the results of the present study show that P wave morphology is determined by right atrial activation. Functional interatrial block appears to be a likely mechanism for this phenomenon.     

Pharmacological therapy of atrial fibrillation and atrial flutter

BACKGROUND: Despite the increasing availability of nonpharmacological treatment options for atrial fibrillation, drug therapy targeted at restoration and maintenance of sinus rhythm, or aimed at symptomatic ventricular rate control remains the mainstay of therapy for the majority of patients. METHOD: Available data suggest that these two treatment approaches yield similar responder rates with regard to symptomatic improvement. RESULTS: Detailed results from major prospective studies investigating the prognostic effects of different atrial fibrillation treatment modalities are expected to become available soon. At present, however, the choice of the primary treatment strategy, i.e. rate control or rhythm control, still remains upon the clinical decision and expertise of the treating physician. Cardioversion by means of external biphasic shock delivery has shown to effectively convert atrial fibrillation to sinus rhythm in more than 90% of patients. Pharmacological cardioversion, in contrast, has a far lower success rate and may be followed by severe complications mandating in-hospital administration with the majority of drug regimens. For the maintenance of sinus rhythm, the proarrhythmic side effects of Class I antiarrhythmic drugs currently limit their use to those patients without any structural heart disease. Clinical investigation of newer "pure" Class III drugs have shown to excite considerable prolongation of ventricular repolarization duration resulting in a significant risk for torsade-de-pointes tachycardia. Betablockers are beneficial in many clinical situations associated with the occurrence of atrial fibrillation, such as heart failure, arterial hypertension and coronary artery disease. These substances, however, do not seem to improve cardioversion rates and their effect in maintaining sinus rhythm is only moderate. Patients with structural heart disease in whom maintenance of sinus rhythm is strongly desired, therefore, are left to amiodarone therapy. The cardiac safety profile as well as the proven effectiveness are unsurpassed by any other available drug at present. This paper reviews major studies published during the last decade implementing recent guidelines regarding pharmacological rate control, cardioversion and maintenance of sinus rhythm and the approach towards patients suffering from paroxysmal atrial fibrillation.     

心房颤动与心房重构的最新进展

心房颤动（房颤,AF）是引起心血管发病和死亡的重要原因.房颤是常见的由一系列心脏疾病引起心房重构的终点事件,其本身也能引起心房重构从而促进心律失常的发展[1].随着人们对心房重构的机制及其在房颤进展中作用的逐渐认识,对离子通道调控机制和作用靶点的研究也有了较深入的发展.本文将重点综述这方面的进展.     

心房肌细胞凋亡及凋亡相关基因在房颤心房重构中的意义

目的 分析风湿性心脏病患者房颤发生与发展的特点，探讨心房肌细胞凋亡以及凋亡相关基因表达变化在房颤心房重构中的意义。 方法 统计分析瓣膜置换手术25例患者临床资料。根据心电图资料分为窦性心律组（10例）和房颤心律组（15例）；术中取右心房组织，行Masson染色及天狼猩红染色，计算胶原容积分数（CVF）评价心房纤维化情况；运用TUNEL染色，荧光显微镜下观察两组细胞凋亡差异；用RT-qPCR检测两组样本凋亡相关基因的表达。 结果 与窦律组比较，房颤组患者LADd和RADd显著增大（均P < 0.01），LVEF显著降低（P < 0.01）、CVF显著增大（P<0.05）、细胞凋亡率显著增高（P < 0.05）、TP53，BAX，Slug-SNAI2基因表达率显著增高（P < 0.05），而BCL-2，BPM4的表达显著降低（P < 0.05）。Pearson相关分析显示LADd、RADd、心房细胞凋亡率和CVF之间存在相关性。 结论 心房细胞的凋亡在心房重构纤维化形成过程中发挥重要作用，其机制与心肌细胞死亡后纤维组织代替性修复有关，调控心房肌细胞凋亡有望改善心房纤维化的形成。