心房颤动患者心房组织中差异表达miRNA的初步研究

目的：应用基因芯片技术研究心房颤动（房颤）患者心房组织中miRNA的表达谱,分析差异表达的miRNA,为进一步研究miRNA在房颤发生、发展中的作用奠定基础。方法：采用miRNA基因芯片技术检测房颤患者和非房颤患者心房组织样本中miRNA的表达水平;采用实时定量PcR（quantitativereal,timePCR,qRT．PCR）对部分差异表达的miRNA进行验证。结果：MiRNA基因芯片分析结果显示,与非房颤组织相比,房颤组织中差异表达的miRNA共有26个,其中16AmiRNA表达上调,10个miRNA表达下调。qRT．PCR验证结果与芯片结果相一致。结论：MiRNA在房颤患者心房组织中存在差异性表达。     

MPO、MMP-2和MMP-9在兔房颤模型心房肌中的表达变化

目的:观察兔房颤模型心房肌组织髓过氧化物酶(MPO)、基质金属蛋白酶(MMP)-2和MMP-9的表达,并探讨三者与房颤时心房结构重构的关系。方法:20只新西兰大白兔,开胸后于左心房植入起搏电极,随机分为2组:快速心房起搏组(RAP组)以600 min-1的频率快速起搏心房3周;假手术组(sham组)不予起搏。起搏前、后行超声心动图检查评价心房和心室的结构和功能,行心房burst刺激检测房颤诱发率;起搏后采用Masson染色评价心房的间质纤维化程度,采用RT-q PCR和Western blot检测心房MPO、MMP-2和MMP-9 mRNA和蛋白的表达水平。结果:起搏3周后,与sham组相比,RAP组兔左心房明显扩张伴收缩功能障碍,左心室的结构和功能变化不明显;RAP组房颤诱发率和间质纤维化百分比均明显增加,且心房MPO、MMP-2、MMP-9 mRNA和蛋白的表达明显增加。结论:持续快速心房起搏兔房颤模型会出现明显心房结构重构,心房MPO、MMP-2和MMP-9表达上调可能是其潜在的分子机制。     

心房颤动患者心房Ⅰ型胶原重构与左心房扩大

目的：探讨心房颤动患者心房Ⅰ型胶原重构与左心房扩大在房颤发病机制中可能的作用以及它们之间的关系。方法:取24例心脏病患者的右心耳组织(房颤12 例,为房颤组；窦性心律12 例，为窦律组)。（1）HE染色，观察房颤组与窦律组心肌纤维以及细胞核、细胞外基质的差异。（2）免疫组化染色，在普通显微镜下观察窦律组与房颤组心房Ⅰ型胶原并使用图像分析系统分析2组的胶原含量分数（collagen volume fraction, CVF），统计2组间Ⅰ型胶原含量分数（CVF-Ⅰ）的差异。（3）〖JP+1〗对CVF-I与左房直径进行Pearson相关分析。结果:(1)房颤组CVF-Ⅰ高于窦律组(CVF-I: 9.29 ±0.85 vs 6.90±1.47, P<0.01)；（2）房颤组心房大于窦律组（6.16±1.01 vs 4.47±0.99， P<0.01）；（3）心房大小与Ⅰ型胶原含量不存在相关性（r=0.33, P>0.05）。 结论:房颤患者的心房纤维化程度增加、左心房扩大，纤维化与左房扩大可能通过一定的途径，直接或间接参与了房颤的发病过程。     

螺内酯对慢性房颤模型兔心房结构重构的影响

目的:探讨螺内酯(SP)对慢性房颤模型兔心房结构重构的影响及其可能的机制。方法:新西兰兔开胸后于左心房植入起搏电极,随机分为快速心房起搏组(RAP组)、螺内酯组(RAP+SP组)和假手术组(sham组)。RAP组和RAP+SP组持续心房起搏3周,分别给予安慰剂和螺内酯20 mg·kg~(-1)·d~(-1)灌胃,sham组不起搏,不给药。起搏前、后评价心房结构和功能,检测房颤诱发率;起搏后评价心房间质纤维化程度,检测心房胶原蛋白(collagen)Ⅰ、collagenⅢ、基质金属蛋白酶(MMP)-2和MMP-9的表达水平。结果:起搏3周后,与sham组相比,RAP组和RAP+SP组兔左心房明显扩张且伴收缩功能障碍;RAP+SP组与RAP组相比,左房结构和功能无明显差异。Sham组、RAP组和RAP+SP组各7只兔分别有0只、7只、5只诱发持续性房颤。与sham组相比,RAP组和RAP+SP组兔心房纤维化程度及collagenⅠ、collagenⅢ、MMP-2和MMP-9的蛋白表达水平明显增加;RAP+SP组与RAP组相比,心房纤维化程度和上述蛋白表达水平均下降(P0.05)。结论:螺内酯能够抑制慢性房颤模型兔心房间质纤维化和胶原蛋白表达,抑制心房结构重构,这可能与螺内酯抑制心房MMP-2和MMP-9蛋白的表达有关。     

机械力敏感离子通道Piezo1参与高血压诱导心房纤维化的机制研究

目的:利用小鼠心房成纤维细胞探讨机械敏感离子通道Piezo1在调控高血压所致心房纤维化,进而导致房颤中的作用及可能机制.方法:采用酶消化法分离培养6～8周龄雄性C57BL/6小鼠的原代心房成纤维细胞,并采用课题组自制的加压装置(专利号201420109263.1)建立高血压模型,Western blot比较不同静水压(...     

心房纤维化与组织结构重构:转化生长因子β1等多种神经体液介质的作用

背景:越来越多研究表明,心房纤维化是多种神经体液介质相互作用引起的,其中包括转化生长因子β1、肾素-血管紧张素-醛固酮系统、半乳糖凝集素3、炎症递质、松弛素等。目的:探讨上述神经体液介质与心房纤维化的关系及在心房结构重构及房颤发生发展中的作用。方法:应用计算机检索万方数据库及Pub Med数据库2000至2014年文献,中文检索词为"心房纤维化,结构重构,房颤,转化生长因子β1,肾素-血管紧张素-醛固酮,半乳糖凝集素3,炎症,松弛素";英文检索词为"myocardial fibrosis,Structural remodeling,Atrial fibrillation,RAAS,Galectin-3,Inflammatory mediators,relaxin",依据纳入排除标准选择42篇文献进行归纳总结。结果与结论:通过分析影响心房纤维化的诸多因素,可以发现促进纤维化发生的各因子间并不是绝对孤立的,而是以一定方式相互增强或相互抑制的,其中转化生长因子β1在各种机制中起着核心作用。各个信号传导途径有不同的侧重,各个信号途径之间亦存在着交叉作用,加深了心房纤维化发病机制的复杂性。心房纤维化会导致局部区域的传导异质性,引起单向阻滞和多子波折返,促进房颤发生。     

芳香烃受体在心房颤动患者心房组织中的表达及意义

目的:检测芳香烃受体(AhR)在风湿性心脏病(风心病)心房颤动患者右心耳组织中的表达,探讨其在心房纤维化中的作用及意义。方法:取风心病换瓣手术患者的右心耳组织为实验组,其中风心病窦性心律组25例和风心病慢性房颤组11例;取先天性心脏病(先心病)心脏手术患者的右心耳组织12例作为对照组。采用Masson染色法检测右心耳组织胶原含量,采用免疫组化技术检测AhR、AhR核转位蛋白(ARNT)和CYP1A1蛋白的表达和分布,采用实时荧光定量PCR检测AhR、ARNT和CYP1A1的mRNA表达,采用Western blot检测AhR、ARNT和CYP1A1的蛋白表达。结果:与先心病组相比,风心病窦律组和风心病慢性房颤组胶原含量和AhR、ARNT、CYP1A1的表达明显增高;与风心病窦律组相比,风心病慢性房颤组胶原含量和AhR、ARNT、CYP1A1的表达明显增高(P0.05)。结论:风心病患者心房组织中AhR的表达与纤维化程度相关;AhR/ARNT/CYP1A1在风心病患者中表达增加,可能参与风心病心房纤维化的发生发展。     

房颤患者血清对心肌成纤维细胞趋化运动的影响

目的: 研究心肌成纤维细胞的运动特性,以及房颤与非房颤患者血清对成纤维细胞趋化运动诱导能力的差异。方法: 用胰酶和胶原酶消化、差速贴壁法培养新生SD大鼠的心肌成纤维细胞,取3-4代采用Transwell装置检测房颤组血清与非房颤组血清诱导成纤维细胞运动的能力差异。结果: 在各组血清的趋化诱导作用下,与对照组相比,迁移至下室的细胞数明显增多。其中持续性房颤组最多,非房颤房性心律失常组明显高于阵发性房颤组,对照组细胞数最少,各组比较均具有显著差异。Logistic回归分析表明,迁移至滤膜下的细胞数与左房直径以及房颤有相关性。结论: (1)各组血清的趋化诱导能力高于对照组,不同组间的差异说明心房纤维化是一个慢性、隐匿、迁延的过程。以修复为目的的成纤维细胞迁移浸润数量间接反映了心肌损伤的存在、范围和程度。(2)迁移浸润的细胞数变化先于左房直径变化,提示房颤和左房直径增大的正相关关系可能并非直接的因果关系,心房肌损伤后的纤维化可能参与其中。     

中介素与高血压合并房颤患者心房纤维化的关系

观察中介素(IMD)在高血压合并房颤患者的变化及与心房纤维化的关系。从2010年6月~2011年6月在四川大学华西医院心内科门诊随访的患者中,筛选出符合要求的受试者150例参加研究。其中包括单纯高血压组(50例),高血压合并阵发性房颤组(48例),高血压合并持续性房颤组(52例)。对受试者完善病史收集及体格检查,进行心脏彩超检查,酶联免疫吸附法测定血浆IMD和转化生长因子β-1(TGF-β1)水平。试验结果显示:1血浆IMD、TGF-β1、左房直径(LAD)水平在三组间比较,差异有统计学意义且分布趋势一致,均是高血压合并房颤组高于单纯高血压组,且持续性房颤组高于阵发性房颤组。2相关性研究结果显示IMD与TGF-β1呈正相关(r=0.51,P0.001),IMD与LAD呈正相关(r=0.59,P0.001),TGF-β1与LAD呈正相关(r=0.57,P0.001);偏回归分析显示IMD与TGF-β1呈正相关(标准系数β=0.31,P0.001),IMD与LAD呈正相关(标准系数β=0.40,P0.001),TGF-β1与LAD呈正相关(标准系数β=0.31,P0.001)。结果提示,随房颤进展心房结构纤维化逐渐加重,IMD可能抑制了心房肌纤维化的病理生理过程。     

钙激活蛋白酶系统与慢性房颤犬心房重构关系的研究

目的： 探讨慢性房颤犬心房肌钙激活蛋白酶（calpain）系统表达水平的改变及其与心房重构的相关性。方法： 17只杂种犬随机分为心房颤动组（11只）和对照组（6只），于起搏前后均进行经胸超声心动图检查，测量舒张期左房内径。房颤组经颈外静脉将电极置入右心耳快速起搏（400 beats/min）8周复制房颤模型，开胸取心房组织，测定心房肌Ca2+浓度，用荧光实时定量PCR和Western blotting技术检测calpain及其抑制剂calpastatin mRNA和蛋白的表达量。结果： 房颤组心房肌Ca2+浓度升高，左房内径显著大于起搏前及对照组(P<0.05)，房颤组和对照组比较犬心房肌calpainⅠ、calpainⅡmRNA表达无显著差异(P＞0.05)，房颤组calpastatin mRNA表达明显高于对照组(P<0.05)；房颤组calpainⅠ、calpainⅡ蛋白表达明显高于对照组(P<0.05)，calpastatin蛋白表达明显低于对照组(P<0.05)。CalpainⅠ、calpainⅡ蛋白表达水平与左房内径呈显著正相关(r=0.53，r=0.67,P<0.05)，calpastatin蛋白表达水平与左房内径呈显著负相关(r=-0.74，P<0.05)。结论： 房颤所引起calpain系统的蛋白表达改变，使calpain/calpastatin系统相互间作用失衡，造成多种蛋白被降解可能是心房重构的重要机制。     

经食管心房调搏诱发阵发性房颤20例分析

目的 探讨经食管心房调搏诱发阵发性房颤的电生理特性及临床意义。方法 采用经食管心房起搏诱发阵发性房颤患者20例（观察组）与无诱发房颤正常人20例（对照组）的电生理资料比较，结果 与对照组比较，观察组最大P波时（Pmax）、心房有效不应期（ERPA）、心房相对不应期区域（ZRRPA）、最大房间传导时间[（S2-A2）max]、早搏刺激的房间延缓（IACD）差异有非常显著意义（P〈0．001）．结论。诱发阵发性房颤的电生理学改变明显，食管心房调搏简便安全，对预测房颤具有一定价值。     

微小RNAs与心房颤动

心房颤动是临床最常见的慢性持续性心律失常,具有进行性、自我延续性的特点.MicroRNAs是新发现的基因表达调控因子,由长约22个核苷酸的单链RNA分子构成.MicroRNAs在控制房颤方面的潜在作用最近才开始研究,这些研究结果有助于了解房颤的分子机制.此综述简要叙述microRNAs的特点和功能、房颤的重构机制以及它...     

慢性房颤病人的AFW研究

利用房颤波谱分析系统（ASpectraAnalysisSystemforAtrialFibrillationWaves，简称AFW）对慢性持续心房颤动患者进行研究，其目的是评价该系统的临床实用价值。     

Assessment of atrial electromechanical interval using echocardiography after catheter ablation in patients with persistent atrial fibrillation

We sought to investigate variation of atrial electromechanical interval after catheter ablation procedure in patients with persistent atrial fibrillation using pulse Doppler (PW) and pulse tissue Doppler imaging (PW-TDI). A total of 25 consecutive in-patients with persistent atrial fibrillation, who restored sinus rhythm after ablation procedure, were recruited in our cardiac center. Echocardiography was performed on each patient at 2 hours, 1 day, 5 days, 1 month and 3 months after the ablation therapy, and atrial electromechanical delay was measured simultaneously by PW and PW-TDI. There was no significant difference between PW and TDI in measuring atrial electromechanical delay. However, at postoperative 2 hours, peak A detection rates were mathematically but nonsignificantly greater by PWTDI than by PW. Second, there was a significant decreasing trend in atrial electromechanical interval from postoperative 2 hours to 3 months, but only postoperative 2-hour atrial electromechanical interval was significantly greater than atrial electromechanical interval at other time. Lastly, patients without postoperative 2-hour atrial electromechanical interval had a significantly longer duration of atrial fibrillation as compared to those with postoperative 2-hour atrial electromechanical interval, by the PW or by PW-TDI, respectively. In patients with persistent atrial fibrillation, atrial electromechanical interval may decrease significantly within the first 24 hours after ablation but remain consistent later, and was significantly related to patients' duration of atrial fibrillation. Atrial electromechanical interval, as a potential predicted factor, is recommended to be measured by either PW or TDI after 24 hours, when patients had recovered sinus rhythm by radiofrequency ablation.     

Cerebrovascular accidents differ between patients with atrial flutter and patients with atrial fibrillation

IntroductionFew studies have explored the potential impact of atrial flutter (AFl) on ischaemic stroke (IS) outcome. The aim of the present study was to compare the clinical course of IS in patients with AFl and patients with atrial fibrillation (AF).Material and methodsA retrospective analysis of patients consecutively admitted to a tertiary care centre between 2013 and 2015 due to IS or transient ischaemic attack with permanent AFl or permanent or persistent AF was performed.ResultsThe study groups consisted of 528 patients, including 490 (92.8%) patients with AF and 38 (7.2%) patients with AFl. The mean age and prestroke CHA2DS2-VASc scores were similar between the patients with AFl and those with AF. Most IS cases in the AF group were classified as cardioembolic strokes (74.9% vs. 39.5% in AFl, p < 0.01), and lacunar strokes were the most common in the AFl group (47.4% vs. 14.3% in AF, p < 0.01). The multivariable analysis revealed that the presence of AF (OR = 8.6, 95% CI: 1.2–57, p = 0.02), lacunar stroke (OR = 0.1, 95% CI: 0.03–0.31, p < 0.001), baseline Rankin scale score (OR = 16.6, 95% CI: 9.8–28), lack of prestroke therapeutic anticoagulation (OR = 6.1, 95% CI: 1.1–33), diabetes (OR = 2.9, 95% CI: 1.3–6.5, p < 0.01), chronic heart failure (OR = 14.2, 95% CI: 5.8–34, p < 0.001), and current smoking (OR = 0.92, 95% CI: 0.39–0.99, p < 0.01) were significantly associated with the stroke outcome.ConclusionsDisabling or fatal IS was observed less often in patients with AFl than in patients with AF. This finding can possibly be explained by the more frequent occurrence of lacunar strokes in the AFl group compared with that in the AF group.     

Sample entropy of the main atrial wave predicts spontaneous termination of paroxysmal atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. In the first stages of the disease, AF may terminate spontaneously and it is referred as paroxysmal atrial fibrillation (PAF). In this respect, the prediction of PAF termination or maintenance could avoid unnecessary therapy and contribute to take the appropriate decisions on its management. The aim of this work is to predict non-invasively the spontaneous termination of PAF episodes by analyzing the variation of atrial activity (AA) organization. The organization increases as a consequence of the decrease in the number of reentries wandering the atrial tissue before termination. The analysis has been carried out by applying sample entropy, which is a non-linear organization estimator, to surface electrocardiogram (ECG) recordings. Synthetic signals were used in order to evaluate the notable impact of noise in AA organization estimation. Therefore, to reduce noise, ventricular residues and enhance the fundamental features of AA, the main atrial wave (MAW) was extracted making use of selective filtering. Through MAW organization estimation applied to real ECGs, 95% (19 out of 20) of the learning PAF recordings and 90% (27 out of 30) of the test episodes were correctly predicted. As a consequence, the MAW organization analysis from surface ECGs can be considered as a promising tool to predict spontaneous PAF termination.     

Primary left atrial fibrosarcoma

An elderly female with refractory cardiovascular symptoms due to functional mitral stenosis secondary to a primary left atrial fibrosarcoma is described. The symptoms are often nonspecific and most of the patients present first time with hemodynamic compromise. A high index of suspicion is essential for the early diagnosis of these highly malignant cardiac tumors because of their rarity, a wide spectrum of nonspecific symptoms and poor survival.     

Fibroblast growth factor-21 is positively associated with atrial fibrosis in atrial fibrillation patients with rheumatic heart disease

Objective: Fibroblast growth factor-21 (FGF-21) has been discovered as a strong hormone, plays an important role in lipid metabolism, glucose metabolism, associated with several diseases such as obesity, metabolic syndrome, diabetes mellitus, and cardiovascular events; however, no evidence is available concerning the relationship of FGF-21 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD). Methods: Twenty-four rheumatic heart disease patients were divided into two groups, 12 cases with AF and 12 cases with sinus rhythm (SR). Clinical characteristics and blood samples were collected before surgery; right atrial appendage samples were taken in the surgery of valve replacement. HE staining was performed to determine cross-sectional area of atrial myocytes; Masson stained sections and mRNA levels of cardiac fibrosis biomarkers were used to evaluate the degree of cardiac fibrosis; the level of FGF-21 was evaluated via enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and real-time polymerase chain reaction (PCR). Results: Compared with SR group, cross-sectional area of atrial myocytes and collagen volume fraction were significantly increased in the atrial tissue of AF group. The distribution of FGF-21 in the AF group was remarkably higher than SR group. In addition, plasma and mRNA levels of FGF-21 in atrial tissue of AF showed the same trend as the result of immunohistochemistry. Using linear correlation analysis, the expression level of FGF-21 was found to be positively related to the degree of atrial fibrosis. Conclusion: FGF-21 might involve in the development and maintenance of atrial fibrosis in atrial fibrillation with rheumatic heart disease, and FGF-21 could be used as a novel biomarker to evaluate myocardial fibrosis in the future.     

Anatomical features and clinical importance of left atrial diverticula

To assess the anatomical features and clinical importance of left atrial diverticula and atrial accessory appendages in patients undergoing cardiac computed tomography with multidetector computed tomography. A total of 1305 consecutive patients (385 female, 29.5%; 920 male, 70.5%) were assessed using electrocardiogram‐gated computed tomography between May 2010 and June 2013. The anatomical features and the prevalences of left atrial diverticula and left atrial accessory appendages were retrospectively assessed by four radiologists. The relationships between the prevalence and size of the diverticula and the age and gender of the patients were assessed. Among the 1305 patients, 610 (46.7%) exhibited 708 left atrial diverticula, and 62 (4.8%) exhibited left atrial accessory appendages. The most common locations of the left atrial diverticula were the right anterior superior wall (n = 328, 46.3%) and the lateral superior wall (n = 96, 13.5%). In addition to classical cystic and tubular diverticula, 49 (3.7%) of the patients exhibited mixed (cystic‐tubular), conical, or hook‐shaped diverticula and diverticular forms containing mural calcifications. There was no significant relationship between the prevalence of diverticula and the age and gender of the patients (P > 0.05). In addition to tubular and cystic diverticula, the left atrial wall can host different diverticular forms (such as mixed, conical, calcific, and hook shaped). It could be beneficial to assess the left atrium using MDCT to determine the source of emboli in cryptogenic embolism and to reduce complications associated with interventional procedures performed for left atrial arrhythmias. Clin. Anat. 27:738–747, 2014. © 2013 Wiley Periodicals, Inc.