氯通道CIC-1、CIC-2在人心房肌的表达及与心房颤动的关系

目的研究氯通道CIC-1和CIC-2基因在人心房组织的表达及与心房颤动（AF）的关系。方法将71例风湿性心瓣膜病接受换瓣手术患者分为三组，窦性心律（SR）组31例，阵发性房颤（PAF）组7例，慢性房颤（CAF）组33例，于术中获取右心耳组织，应用半定量逆转录-聚合酶链反应（RT—PCR）检测心房组织CIC-1和CIC-2的mR—NA相对含量。结果（1）CIC—1、CIC-2基因在人心房组织有表达。②与SR组比较，PAF组CIC-1的mRNA表达增加但无统计学意义（1．05±0．22vs1．01±0．13，P〉0．05），CAF组的表达明显增加（1．25±0．18vs1．01±0．13，P〈0．001），CAF组较PAF组亦明显增加（P〈0．01）。CIC-1的mRNA表达水平与左房内径、AF持续时间呈正相关[（r=0．344，P=0．003）（r=0．405，P〈0．001）]。③与SR组比较，PAF组CIC-2的mRNA表达无增加（1．03±0．14vs1．04±0．15，P〉0．05），CAF组的表达明显增加（1．26±0．13vs1．04±0．15，P〈0．001），CAF组较PAF组亦明显增加（P〈0．01）。CIC-2的mRNA表达与左房内径、AF持续时间呈正相关[（r=0．441，P〈0．001）（r=0．331，P=0．0C15）]。结论AF患者CIC-1、CIC-2的mRNA表达水平的增加可能是心房肌电重构的分子基础。     

心房颤动患者心房组织囊性纤维化跨膜转运调节体氯通道基因表达

目的探讨心房颤动(简称房颤)患者心房组织囊性纤维化跨膜转运调节体(CFTR)氯通道基因的表达。方法应用半定量逆转录多聚酶链反应(RT-PCR)比较窦性心律(SR)组(n=31)、阵发性房颤(PAF)组(n=7)和慢性房颤(CAF)组(n=33)患者心房组织CFTR氯通道基因的表达。结果与SR组相比,PAF组CFTR的mRNA表达有增加但未达到统计学意义(P>0.05),CAF组的表达明显增加,CAF组较PAF组亦明显增加(1.20±0.12 vs1.08±0.18,P<0.05)。CFTR的mRNA表达与左房内径呈正相关(r=0.312,P=0.008)。结论慢性房颤患者心房组织CFTR氯通道基因表达上调,可能在房颤心房电重构中起作用。     

心房颤动电重构心房肌Ca2+调控蛋白异常与解剖学改变关系的研究

目的探讨心房肌Ca2+调控蛋白(calcium handling proteins)在心房颤动(atrial fibrilation,AF)电重构中的作用及与解剖学结构改变的关系.方法测定10例慢性AF患者和6例对照组心房肌Ca2+含量和细胞膜L型Ca2+通道(L-type calcium channel)、肌浆网钙泵(sarcoplasmic reticulum calciumadenodinetriphosphatase,SR Ca2+-ATPase)、磷酸受纳蛋白(phospholamban)、兰尼碱受体(ryanodine receptor)和肌集钙蛋白(calsequestrin)的信使核糖核酸(messenger ribonucleic acid,mRNA)表达;测量AF患者左、右心房内径、二尖瓣口面积和肺动脉收缩压.结果与对照组比较,AF患者心肌细胞内Ca2+含量增加[(1 330±770)μg/ml vs(302±31)μg/ml,P<0.01];细胞膜L型Ca2+通道、SR Ca2+-ATP ase和兰尼碱受体mRNA下调[(0.65±0.30)v(0.97±0.19),P<0.01;(0.73±0.13)vs(1.10±0.11),P<0.001;(0.71±0.25)vs(0.90±0.13),P<0.05].SRCa2+-ATPasemRNA表达与左心房内径中度负相关(r=-0.56,P<0.05);与二尖瓣口面积正相关(r=0.70,P<0.05);细胞膜L型Ca2+通道mR-NA表达与二尖瓣口面积显著正相关(r=0.84,P<0.01).结论频率相关的细胞内Ca2+超负荷可能是AF电重构的始动因素,心房肌Ca2+调控蛋白异常是Ca2+超负荷的分子生物学机制,Ca+调控蛋白mRNA表达异常与左心房解剖学改变之间存在内在联系.     

细胞凋亡在慢性风湿性心房颤动左房结构重构中的作用

目的探讨细胞调亡在心房颤动(AF)患者心房结构重构中的作用;检测风湿性心脏病患者左房中caspase-3和Bc l-2的蛋白含量及其细胞凋亡的发生率。方法选择风湿性心脏病患者43例,其中窦性心律(SNR)组15例,阵发性AF(PAF)组8例,慢性AF(CAF)组20例。在外科手术前行超声心动图检查,手术中取左房组织,应用免疫印迹法测定患者的caspase-3和Bc l-2的蛋白含量;应用TUNEL法检测心房肌细胞凋亡,计算其凋亡指数(AI)。结果①与SNR组比较,CAF组caspase-3的蛋白含量增加到394%±99.4%(P<0.001);Bcl-2蛋白含量则降低到32.8%±15.9%(P<0.001),而PAF组的各蛋白含量则无明显变化;②CAF组左房心肌细胞AI为24.6%±9.1%,明显高于SNR组和PAF组(P<0.01)。③CAF组caspase-3的蛋白含量及AI分别与左房内径、AF持续时间呈明显正相关;Bc l-2的蛋白含量与左房内径和AF持续时间呈明显负相关(P均<0.05)。④AI与caspase-3、Bc l-2的蛋白含量分别呈正、负相关;P均<0.05。Caspase-3的蛋白含量与BCL-2的呈负相关,P<0.05。结论CAF时,caspase-3蛋白表达增加和Bc l-2蛋白表达降低导致的细胞凋亡可能是AF发病的重要机制之一。     

整合素β1在心房颤动心房结构重构中的作用

目的探讨整合素β1在慢性心房颤动(房颤)心房结构重构中的作用。方法选择30例经心外科手术患者的右心耳肌组织,按有无房颤病史分为房颤组(15例)和无房颤组(15例)。Masson染色测定两组心房组织胶原容积分数(CVF);RT-PCR方法检测整合素β1 mRNA的表达;Western blot检测整合素β1蛋白的表达。结果与无房颤组比较,房颤组患者左心房直径增大[(4.96±0.50)mm vs (4.15±1.04)mm.P<0.05];房颤组患者CVF较无房颤组明显升高(42.38±9.79 vs 11.67±3.35,P<0.01);与无房颤组比较,房颤组患者整合素β1 mRNA及蛋白表达上调(0.43±0.03 vs 0.36±0.02,P<0.05;1 724.33±91.07 vs 853.13±30.34,P<0.01)。整合素β1蛋白与左心房直径(r=0.879,P<0.01)、房颤持续时间(r=0.830,P<0.01)及CVF(r=0.770,P<0.05)呈正相关。结论慢性房颤时,整合素β1基因及蛋白表达上调;整合素β1可能参与房颤时心房的结构重构。     

心房颤动患者心房组织钾通道Kir2.1和Kir3.4的基因表达

目的　研究心房颤动 (房颤 )患者心房组织钾通道Kir2 1和Kir3 4基因表达的改变。方法　将 4 6例风湿性心瓣膜病接受换瓣手术患者分为 3组 ,窦性心律 (SR)组 18例 ,阵发性房颤 (PAF)组7例 ,慢性房颤 (CAF)组 2 1例 ,应用半定量逆转录 聚合酶链反应 (RT PCR)技术 ,检测心房组织Kir2 1、Kir3 4mRNA表达。结果　和SR组相比 ,Kir2 1mRNA在CAF组中的表达增加具有显著性 (P <0 0 1) ;Kir3 4mRNA在PAF组 (P <0 0 5 )和CAF组 (P <0 0 1)中的表达均显著减少。结论　风湿性心瓣膜病伴房颤患者Kir2 1mRNA表达上调和Kir3 4mRNA表达下调 ,可能分别是IK1 上调、IKACh下调的分子基础 ,Kir3 4mRNA表达水平的减少可能是机体为拮抗房颤电重构时有效不应期缩短的代偿机制之一。     

左室功能减退窦性心律患者心房肌短暂外向钾电流mRNA表达的变化

探讨心力衰竭患者易患心房颤动(AF)的可能发生机制之一。采集左室功能减退组患者(n=18例)和左室功能正常组患者(n=18例)的右心耳组织,应用逆转录聚合酶链反应技术(RTPCR)以3磷酸甘油醛脱氧酶(GAPDH)为内参照,测定心房肌KV4.3α的mRNA表达水平,反应心房肌短暂外向钾电流(Ito1)的变化。结果:与左室功能正常组相比,左室功能减退组心房肌KV4.3α的mRNA表达减低46.20%(0.83±0.07vs0.45±0.09,P<0.01)。结论:左室功能减退患者心房肌KV4.3αmRNA表达降低。     

原发性高血压并发阵发性房颤心房结构和功能的研究

目的应用声学定量(AQ)技术,探讨高血压病有无阵发性房颤(PAF)时左心房结构和功能的变化并筛选高血压病PAF的超声危险因素。方法83例高血压病患者按PAF、有无分为两组,对比分析两组的一般临床特征及声学定量指标。结果PAF组左房内径、左房内径指数、各时相左房容积(EDV、ESV、EREV、OAEV)均明显大于无PAF组,与无PAF组相比,PAF组左房储存器容积(RV)显著增大,LAEF明显降低[RV:(64.61±18.64)vs(49.35±18.43)ml,P<0.001;LAEF:(0.44±0.16)vs(0.54±0.15),P<0.01)。结论与高血压无PAF者相比,高血压伴。PAF者左房容积增大,储存器功能增强,左房助力泵功能减低;左房增大和左房收缩功能减低是高血压病发生PAF的危险因素。     

心房颤动患者离子重构的分子基础

目的　研究心房颤动 (AF)患者离子重构的分子基础。方法　以先天性心脏病 (CHD)和风湿性心脏病 (RHD)持续窦性心律 (SR)患者为对照 ,应用半定量RT PCR法检测RHD伴阵发性AF(PAF)慢性AF 6个月 (AF 6M )和慢性AF >6个月 (AF >6M )患者心房肌L 型电压依赖钙通道α1c亚基 (LVDCCα1c)、电压依赖KV4 3钾通道α亚基 (VDKV4 3α)和电压依赖钠通道α亚基 (VDSCα)mRNA的表达。结果　SR组内CHD患者与RHD患者LVDCCα1c、VDKV4 3α和VDSCα的mRNA表达差别无明显性 ;与对照组相比 ,各组AF患者VDSCα的表达没有改变 ;LVDCCα1c在AF >6M患者中的表达显著下降 ,而在PAF和AF 6M患者中的表达有不同程度下调 ,但无统计学意义 ;LVDCCα1cmRNA表达与心房率、左、右心房内径成明显负相关 ,并且其表达随AF分数增高逐渐下降 ;单因素协方差分析 (ANOVA)矫正心房内径的影响 ,AF >6M患者α1cmRNA表达仍明显下降 (P <0 0 1)。KV4 3αmRNA在PAF、AF 6M和AF >6M患者中的表达均显著降低。KV4 3钾通道α亚单位mRNA表达与AF分数、左心房内径和平均心房率均成明显负相关 ,经ANOVA剔除左心房内径的影响 ,各组mRNA表达较SR组仍显著下降 (P <0 0 5 )。结论　L 型钙通道和KV4 3钾通道转录水平下调是相应ICaL和Ito1重构的分子基础 ,基因表     

左心耳组织中基质金属蛋白酶-2表达与风湿性心脏瓣膜病手术同期行心房颤动射频消融疗效间的相关研究

目的:探讨左心耳组织中基质金属蛋白酶-2(MMP-2)和金属蛋白酶组织抑制因子-2(TIMP-2)的表达对风湿性心脏瓣膜病(风心病)瓣膜手术同期行心房颤动(房颤)射频消融疗效的影响.方法:风心病瓣膜手术同期慢性房颤射频消融术患者共80例,根据术后6个月随访结果分为房颤消除组(n=56)和房颤未消除组(n=24).以逆转录聚合酶链反应法和蛋白质印迹法检测左心耳组织中MMP-2和TIMP-2的信使核糖核酸(mRNA)和蛋白表达,天狼猩红染色偏振光显微镜观察Ⅰ型和Ⅲ型胶原容量分数(CVF-Ⅰ和CVF-Ⅲ).结果:房颤未消除组心房组织MMP-2的mRNA及蛋白表达较房颤消除组明显增加(126.75±47.67 vs.62.43±31.41,P<0.001;140.33±35.17 vs.82.57±29.56,P<0.001),CVF-Ⅰ也较房颤消除组明显增加(18.16±3.22 vs.11.66±3.38,P<0.001).两组之间TIMP-2的mRNA和蛋白表达及CVF-Ⅲ无明显区别.左心耳组织MMP-2的mRNA和蛋白表达与CVF-I呈显著正相关(r=0.575,P<0.001;r=0.637,P<0.001),左心耳组织中MMP-2的mRNA和蛋白表达与左心房直径也呈显著正相关(r=0.465,P=0.003;r=0.571,P<0.001).结论:左心耳组织MMP-2表达与左心房大小和心房纤维化程度相关并影响瓣膜手术同期射频消融治疗房颤的疗效.     

心房颤动患者心房肌组织CYP11B2的mRNA表达及研究

目的　探讨心房颤动患者心房肌组织醛固酮合成酶 (CYP11B2 )的mRNA表达情况。方法　 38例因心脏疾患住院接受开胸手术的患者 ,男 18例 ,女 2 0例 ,年龄 18～ 77岁 ,平均 (5 1.92± 14 .0 0 )岁。按有无心房颤动病史分为 3组 :窦性心律组 (SR组 ) ,11例 ;阵发性心房颤动组 (pAF组 ,心房颤动持续时间 <6个月 ) ,13例 ;慢性心房颤动组 (cAF组 ,心房颤动持续时间 >6个月 ,14例。半定量聚合酶链式反应技术测定CYP11B2mRNA在心房肌组织中的表达情况。结果　与SR组和 pAF组相比 ,cAF组患者左心房直径明显增大 (分别增大 78.8%和 37.5 % ,P <0 .0 1) ,CYP11B2mRNA表达水平明显升高 (分别升高 81%和 11.8% ,P <0 .0 5～ 0 .0 1) ,并与左心房直径变化显著正相关 (P <0 .0 0 1,r =0 .82 7)。cAF组左心室射血分数明显低于SR组 (P <0 .0 5 )。结论　组织醛固酮增加可能参与了心房颤动发生的介导 ,该作用很可能通过促进心房结构重构来实现。     

心房颤动患者心房组织延迟整流钾通道基因表达的研究

目的 探讨心房颤动（AF）患者心房组织延迟整流钾通道（Kv1、5、HERG、KvLQT1通道）基因表达的变化。方法 以窦性心律组（SR组）为对照，应用逆转录-聚合酶链反应（RT—PCR），以三磷酸甘油醛脱氢酶（GAPDH）为内参照，检测35例风湿性心脏瓣膜病患者右心耳组织Kv1．5、HERG、KvLQT1通道的mRNA表达量。结果 和SR组相比，Kv1．5钾通道mRNA表达在慢性房颤组（CAF组）下降显著，有统计学意义（P〈0．05），在阵发性房颤组（PAF组）差异无统计学意义（P〉0．05）；HERG钾通道和KvLQT1钾通道mRNA表达CAF组和PAF组差异均无统计学意义（P〉0．05）。结论 Kv1．5钾通道转录水平下调可能是相应超速延迟整流钾电流（IKur）重构的分子基础，其基因表达异常是AF电重构的重要环节；HERG钾通道和KvLQT1钾通道在基因转录水平差异无统计学意义，与AF模型快速延迟整流钾电流（IKr）和缓慢延迟整流钾电流（IKs）无变化相符。     

慢性心房颤动患者血清醛固酮水平与胶原合成血清学标志相关

目的探讨慢性心房颤动(简称房颤)患者血清醛固酮水平与胶原合成的血清学标志之间的相关性。方法收集72例慢性房颤患者(房颤组)及50例窦性心律患者(对照组)。用放射免疫法测定血清醛固酮水平,用酶联免疫吸附分析法测定血清Ⅰ型胶原羧基端前肽(Ⅰ型CP)及Ⅲ型胶原前多肽(Ⅲ型NP)的水平。结果房颤组血清Ⅰ型CP水平显著高于对照组(P<0.01),伴左房扩大的房颤患者Ⅰ型CP水平更高(P<0.01),并且血清Ⅰ型CP水平与左房内径呈正相关。两组受试者中血清Ⅲ型NP水平无显著差别。与对照组相比,房颤组血清醛固酮水平显著增高(P<0.01),伴左房扩大的房颤患者醛固酮水平更高。血清醛固酮水平与左房内径及血清Ⅰ型CP水平呈正相关。结论慢性房颤患者血清醛固酮升高,并与血清Ⅰ型CP水平呈正相关,提示过高的醛固酮水平可能参与心房纤维化形成及房颤的维持。     

Paroxysmal atrial fibrillation coincident with cardiac decompensation is a predictor of poor prognosis in chronic heart failure.

BACKGROUND: The prognostic significance of atrial fibrillation (AF) in chronic heart failure (CHF) remains poorly understood. METHODS AND RESULTS: Death and rehospitalizaion for CHF exacerbation for 427 consecutive patients hospitalized from 1996 to 2002 were retrospectively analyzed in relation to cardiac rhythm: sinus rhythm (SR; n=239) or AF (n=188). The AF group was classified according to an Intervention (n=57) or Non-Intervention (n=131) group for defibrillating AF. During the follow-up of 34+/-23 months, there was no significant difference of mortality or morbidity between the SR and AF groups, or between the Intervention and Non-Intervention groups, respectively. However, the Non-Intervention group consisted of 28 patients with paroxysmal AF (PAF), which spontaneously converted to SR during hospitalization, and 103 with chronic AF (CAF). The rehospitalization for CHF exacerbation was significantly higher in PAF than that in CAF and SR (p=0.00005 and 0.002, respectively). Multivariate Cox analysis demonstrated that, PAF, but not CAF, was a predictor of readmission (relative risk 2.30, p=0.004, 95% confidence interval 1.30 to 4.05). CONCLUSIONS: The present data implied that PAF coincident with cardiac decompensation could be a new predictor of prognosis for CHF. The management strategies of AF in CHF should be discussed according to the phenotype of AF.     

Time- and frequency-domain characteristics of atrial electrograms during sinus rhythm and atrial fibrillation

Ablation and Spectral Characteristics of Fibrillation. Background: Complex fractionated atrial electrograms (CFAE) have been considered to be helpful during catheter ablation of atrial fibrillation (AF). The purpose of this study was to analyze the characteristics of CFAEs recorded during sinus rhythm (SR) and AF, and to determine their relationship to perpetuation of AF and clinical outcome. Methods and Results: Antral pulmonary vein isolation (APVI) was performed in 34 consecutive patients (age = 59 ± 10 years) with paroxysmal AF who presented in SR. Time‐ and frequency‐domain characteristics of electrograms recorded from the same sites in the coronary sinus (CS) were analyzed during SR and AF, before and during isoproterenol infusion. There was a modest correlation in fractionation index (FI: change in the direction of depolarization, r = 0.40, P = 0.001) and complexity index (CI: change in the polarity of depolarization, r = 0.41, P = 0.001), but not in the dominant frequency (DF) between SR and AF. There was no relationship between the DF and CI or FI during AF. Isoproterenol was associated with an increase in DF during AF (6.6 ± 0.9 vs 5.1 ± 0.6 Hz, P < 0.001) but had no effect on CI or FI (P = 0.6). A higher CI (58.3 ± 21.0/s vs 38.0 ± 21.0/s, P < 0.01), and FI (123.5 ± 44.8/s vs 75.6 ± 44.6/s, P < 0.01) during AF were associated with a lower likelihood of termination of AF during APVI and a higher probability of recurrent AF after ablation. Ratio of FI during AF to SR was also higher when AF persisted than terminated after APVI (29.7 ± 12.4 vs 19.1 ± 9.7, P = 0.002). However, time‐ or frequency‐domain parameters during SR were not predictive of termination or clinical outcome. Conclusions: Structural and functional properties of the atrial myocardium during AF contribute to electrogram complexity, which may indicate the presence of extra‐PV mechanisms of AF that are not eliminated by APVI. Mapping of complex electrograms in SR is not likely to be sufficient to identify drivers of AF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 851‐857, August 2011)     

Decreased plasminogen activator inhibitor and tissue metalloproteinase inhibitor expression may promote increased metalloproteinase activity with increasing duration of human atrial fibrillation

Introduction: Atrial fibrosis has been shown to concur with the persistence of atrial fibrillation (AF) and is only incompletely reversible, thus counteracting attempts to restore and maintain sinus rhythm (SR). Besides the angiotensin system, the matrix metalloproteinases (MMP) play a major role in the pathogenesis of fibrosis. Thus, the present study investigated changes of the MMP system during the development of human AF.
Methods and Results: Right atrial appendages of 146 patients were excised during heart surgery and grouped according to rhythm (SR vs AF) and AF duration. Hydroxyproline as a surrogate for collagen content and morphometrically determined collagen content increased significantly from SR (14.3 ± 7.7%) to chronic permanent AF (CAF) of 6–24 months (21.2 ± 9.2%, P = 0.02), and CAF of > 60 months (25.3 ± 4.7%, P < 0.01). From SR to paroxysmal and chronic persistent AF (CPAF) and to CAF MMP-2 and MMP-9 activity rose, while their mRNA and protein levels were not altered significantly. Plasminogen activator inhibitor (PAI), an inhibitor of a potent activator of many MMPs, was significantly decreased with increasing duration of AF. In parallel, the mRNA levels of the tissue inhibitors of MMPs TIMP-1 and -2 decreased significantly.
Conclusion: Human atrial fibrogenesis is enhanced with increasing duration of AF: a longer AF duration is associated with elevated atrial interstitial MMP activity, but decreased PAI and TIMP expression.