Enalapril preserves sinus node function in a canine atrial fibrillation model induced by rapid atrial pacing

METHODS AND RESULTS: Seventeen beagles were pretreated with either placebo (group I, n = 9) or enalapril 1 mg/kg/day (group II, n = 8) and paced at 500/min from the right atrial appendage for 4 weeks. Every week, corrected sinus node recovery time (CSNRT) and sinus cycle length (SCL) were measured. Quantitative analysis of interstitial fibrosis (IF) and adipose tissue (AT) in the SN was performed with Masson's trichrome stain, and apoptosis of the sinus nodal cells were detected with terminal deoxynucleotidyl transferase nick end-labeling. In group I, rapid atrial pacing prolonged both CSNRT and SCL. After 4 weeks of pacing, CSNRT and SCL were significantly shorter in group II (CSNRT, 410 +/- 37 msec; SCL, 426 +/- 34 msec) than in group I (CSNRT, 717 +/- 52 msec, P < 0.005; SCL, 568 +/- 73 msec, P < 0.05). Both IF and AT of the SN were greater in group I (IF, 9.7 +/- 1.9%; AT, 32.6 +/- 5.9%) than in seven sham dogs (IF, 2.4 +/- 0.9%, P < 0.05; AT, 4.0 +/- 1.7%, P < 0.05) and in group II dogs (IF, 4.0 +/- 2.0%, P < 0.05; AT, 4.0 +/- 1.7%, P < 0.05). End-labeling assay was positive in three of nine dogs in group I, but negative in group II and sham dogs. CONCLUSIONS: Rapid atrial pacing impaired SN function through IF and AT of the SN. Enalapril prevented these pacing-induced degenerative changes and improved SN function.     

慢性快速肺静脉起搏建立犬持续性心房颤动模型

目的探讨利用慢性快速刺激肺静脉的方法,建立犬持续性心房颤动(简称房颤)模型。方法在15只犬的左上肺静脉放置自制的环状起搏电极,并在左房游离壁缝合一片状标测电极。将肺静脉起搏电极在体外连接自制的脉冲发生器,持续快速起搏(1200次/分)肺静脉。每隔三天进行心房程序电刺激和burst刺激,分析电生理指标,直至房颤维持超过24h。超声心动图测量基础状态和起搏结束后左右房面积等指标。结果11只犬完成研究。在28.2±3.0天内诱发出持续超过24h的房颤,4只不需刺激诱发即发生自发性房颤,5只经程序刺激可发生房颤,2只经burst刺激可发生房颤,持续时间大于24h。超声心动图测量显示起搏结束后心房面积明显扩大(左房:6.9±1.1cm2vs11.7±1.6cm2;右房:4.3±0.8cm2vs7.0±1.2cm2,P均<0.001)。结论慢性快速刺激犬肺静脉建立持续性房颤模型的方法临床模拟性好,可靠易行。     

快速右心房起搏致犬心房迷走神经重构的研究

目的 通过对快速心房起搏犬的神经相关因子的研究,观察右心房快速起搏48 h是否引起神经重构及其在心房颤动(房颤)中的作用.方法 健康杂种犬12只,随机分为房颤组(6只)和对照组(6只).右心房起搏600次/min、持续48 h.通过一种在发芽轴突生长丘中表达的蛋白质(GAP-43)和乙酰胆碱转移酶(CHAT)来了解心脏神经萌发和迷走神经的重构.结果 在房颤犬的左心房、左心耳、右心房和右心耳,GAP-43和CHAT的神经密度同对照组相比明显增高,差异均有统计学意义(P<0.05).此外,房颤犬的右心房GAP-43和CHAT的神经密度与左心房有明显差异(P<0.05),显微镜下显示每个样点心脏神经不均匀分布.结论 48 h持续起搏犬右心房形成阵发性房颤,可见明显的神经萌发和迷走神经重构且不均一分布.     

基质金属蛋白酶在心房颤动犬心房结构重构中的作用

目的 探讨基质金属蛋白酶-9（MMP-9）和组织型基质金属蛋白酶抑制因子-1（TIMP-1）在快速起搏心房颤动（房颤）动物模型心房结构重构中的作用和Ca^2＋超载对MMP-9激活的影响。方法 14只犬随机分为房颤组（n=8）和对照组（n=6），右心房快速起搏（350～450次／min）8周建立房颤动物模型。取左心房组织，采用半定量逆转录聚合酶链反应（RT-PCR）和免疫组织化学法检测MMP-9和TIMP-1 mRNA和蛋白质表达，采用Masson染色测定心房肌组织胶原含量，采用超声心动图测量左心房内径，同时还测定心房肌组织Ca^2＋浓度。结果 与对照组比较，房颤组心房肌胶原含量、Ca^2＋浓度和左心房内径增加（P〈0．05）；房颤组左心房心肌组织MMP-9 mRNA表达升高45％（P〈0．01），蛋白质水平表达增加19．5％（P〈0．001）；TIMP-1 mRNA表达增加46．67％（P〈0．01），TIMP-1蛋白质水平表达下调8．33％（P〈0．01）；MMP-9 mRNA表达与左心房内径、Ca^2＋浓度和心肌胶原含量正相关（P〈0．05）；TIMP-1 mRNA表达与左心房内径、心肌胶原含量和MMP-9 mRNA表达正相关（P〈0．05）。结论 MMP-9／TIMP-1平衡失调可能是慢性房颤心房肌细胞外基质重构和心房扩大的重要分子机制，细胞内Ca^2＋超载可能是MMPs的重要激活途径。     

心外膜左心耳起搏建立山羊心房颤动模型

目的探讨开胸置入高频起搏器建立山羊心房颤动(AF)模型的方法和可行性。方法山羊12只,随机分为实验组(6只)与对照组(6只)。开胸后于左心耳底部置入起搏电极,以400±10次/分连续起搏12周,诱导AF。记录山羊体表心电图变化。连续起搏12周采用光学显微镜、电镜观察左、右房游离壁心肌组织学、超微结构的变化。结果1只山羊术中死亡;5只经连续起搏12周后,出现AF心电图改变。左房游离壁较右房游离壁心肌细胞直径变细;左房游离壁较右房游离壁心肌纤维排列紊乱,润盘受损,心肌纤维溶解明显,线粒体增多、体积变大,内质网模糊、有的出现空泡样等改变更加明显。正常对照组左、右房心肌纤维排列规整。结论心外膜左心耳起搏建立AF动物模型是可靠而易行的方法。     

Induction of atrial fibrillation in mice by rapid transesophageal atrial pacing

Objective: Atrial fibrillation (AF) as an “indicator arrhythmia” for enhanced atrial vulnerability in mouse hearts has not yet been systematically examined. We therefore evaluated a transesophageal rapid atrial stimulation protocol for the induction of AF in C57Bl/6 mice. Methods: 40 C57Bl/6 mice (19 female and 21 male; 5.2 ± 2.1 months; 18 – 27 g) were examined by closed chest transesophageal atrial stimulation. Baseline ECG and electrophysiological parameters, AF-inducing stimulation cycle length (CL) and AF duration were analyzed. Results: The surface ECG demonstrated a significantly faster heart rate in female mice (R-R: 138.7 ± 19.9 ms versus 150.5 ± 15.7 ms, P < 0.05). AF was inducible in 90 % of the population and not inducible in 4 mice, all female (21 % in this subgroup). Mean induction CL was 27.4 ± 7.3 ms. Mean AF duration was 26.9 ± 42.6 s before spontaneous termination. In a subgroup of 4 female and 4 male mice (mean age 7.5 months), successive testing of AF induction showed a range of higher susceptibility to AF at stimulus amplitudes of 3.0 – 4.0 mA and stimulation CLs between 15 – 25 ms. AF induction was observed to be constantly reproducible in the individual animals. No correlation to pacing stimulus length and amplitude was found. Conclusions: This study demonstrates that it is possible to reproducibly induce self-terminating AF and supraventricular arrhythmias in mice by transesophageal atrial burst stimulation. The presented method allowing serial testings of the same animal can be a useful tool in further investigations with transgenic mice and might be helpful in the characterization of underlying genetic or molecular mechanisms of AF. Received: 26 April 2002, Returned for revision: 21 May 2002, Revision received: 17 June 2002, Accepted: 24 June 2002 Correspondence to: J. W. Schrickel, MD     

Ablation of atrial fibrillation using novel 4-dimensional catheter tracking within autoregistered left atrial angiograms

Background- We describe a novel fluoroscopy coregistered, 4-dimensional catheter tracking technology (MediGuide Technology [MGT]) used for treatment of patients with atrial fibrillation. The aim of the study was to investigate (1) the feasibility of nonfluoroscopic catheter manipulation within dynamic left atrial chamber models; (2) the integration of the technology into an established electroanatomical mapping system; and (3) potential clinical impact. Methods and Results- Forty-nine patients received atrial fibrillation ablation using MGT-enabled NavX-EnSite. Matched patients ablated with a conventional NavX-EnSite system served as a control group. MGT was used for the deployment of diagnostic catheters within preacquired cine loops, for nonfluoroscopic chamber mapping within dynamic angiograms, and for 4-dimensional tagging of anatomical landmarks. Integration with the electroanatomical mapping system allowed correction of field distortions and a reference tool to detect and correct map shifts. Catheter ablation was done without MGT because the ablation catheter was not MGT enabled. MGT worked safely and stably in all 49 patients. Catheter deployment within the preacquired cine loops was successfully performed in 45 of 49 (92%) patients. Catheter tracking within dynamic left atrial angiograms allowed nearly nonfluoroscopic creation of NavX-EnSite geometries with subsequent computed tomography model registration in all 49 patients. Overall, MGT significantly reduced total procedural fluoroscopy time (median [quartiles]) from 31 minutes (25, 43 minutes) to 16 minutes (10, 23 minutes) and irradiation dose from 14 453±7403 to 7363±5827 cGy*cm(2) (mean±SD), respectively (P<0.001). Conclusions- MGT is a tracking technology that allows 4-dimensional visualization of dedicated catheters within moving chamber models. Integration of the MGT with an established electroanatomical mapping system provided algorithms to facilitate mapping in the electroanatomical mapping system environment. As a first measurable clinical impact, MGT was able to reduce fluoroscopy exposure by nearly 50%.     

快速起搏心房对犬心房电生理特性改变的研究

目的:研究心房颤动时心房肌的电生理改变。方法:快速持续起搏犬右心房24h制作房颤模型。比较起搏前(P0)、起搏后6h(P6)、12h(P12)和24h(P24)各时段的血压、心房传导速度和房颤波周长(atrial fibrillation cycle length,AFCL)的变化来分析心房肌的电生理改变。结果:起搏后平均动脉血压在P12[(126.06±7.01)mmHg]和P24时[(118.56±8.26)mmHg]较P0[(138.23±5.42)mmHg]明显下降。起搏24h后,P波时间是(78.91±6.21)ms,PA间期是(94±7.89)ms,与起搏前比较有显著延长(P<0.05)。连续快速起搏右心房在P6、P12和P24时的房颤自发维持的时间分别是5~10s、3~5min和15~20min。在起搏前和起搏后不同时间段,左房AFCL明显短于右房AFCL。右房房颤自发持续时间5~10s和15~20min的AFCL分别是(131.86±5.32)ms和(112.45±5.27)ms,P<0.05;左房房颤自发持续时间5~10s和15~20min的AFCL分别是(99.53±4.96)ms和(84.31±2.84)ms,P<0.05。结论:快速心房起搏建立的房颤模型可引起血压进行性下降、心房传导速度减慢和AFCL缩短。     

快速起搏心房对犬心房电生理特性改变的研究

目的:研究心房颤动时心房肌的电生理改变。方法:快速持续起搏犬右心房24h制作房颤模型。比较起搏前(P0)、起搏后6h(P6)、12h(P12)和24h(P24)各时段的血压、心房传导速度和房颤波周长(atrial fibrillation cycle length,AFCL)的变化来分析心房肌的电生理改变。结果:起搏后平均动脉血压在P12[(126.06&#177;7.01)mmHg]和P24时[(118.56&#177;8.26)mmHg]较P0[(138.23&#177;5.42)mmHg]明显下降。起搏24h后,P波时间是(78.91&#177;6.21)ms,PA间期是(94&#177;7.89)ms,与起搏前比较有显著延长(P&lt;0.05)。连续快速起搏右心房在P6、P12和P24时的房颤自发维持的时间分别是5~10s、3~5min和15~20min。在起搏前和起搏后不同时间段,左房AFCL明显短于右房AFCL。右房房颤自发持续时间5~10s和15~20min的AFCL分别是(131.86&#177;5.32)ms和(112.45&#177;5.27)ms,P&lt;0.05;左房房颤自发持续时间5~10s和15~20min的AFCL分别是(99.53&#177;4.96)ms和(84...     

Biatrial pacing for paroxysmal atrial fibrillation: a randomized prospective study into the suppression of paroxysmal atrial fibrillation using biatrial pacing

OBJECTIVES: The purpose of this study was twofold: to assess whether biatrial pacing is superior to single-site pacing and capable of reducing the frequency of episodes of paroxysmal atrial fibrillation (PAF); and to compare pacing of the proximal coronary sinus (PCS) with the distal coronary sinus (DCS) and the effects of sequential or simultaneous biatrial pacing. BACKGROUND: Interatrial conduction abnormalities have a role in the initiation of PAF. Biatrial pacing alters the site and timing of atrial depolarization and may benefit those with drug-resistant PAF. METHODS: Nineteen patients with PAF who were intolerant of or refractory to medication were studied. All received right atrial (RA) and coronary sinus (CS) leads (either PCS or DCS). For three months the pacemaker was set in sensing mode only. Subsequently each patient completed three-month periods in random order in the following modes: RA pacing, CS pacing, biatrial pacing using inter-atrial delays of 15 and 70 ms. RESULTS: Sixteen patients received a benefit from one or more pacing modes. The greatest reduction in PAF episodes was seen during biatrial pacing, especially with leads sited at the high right atrium (HRA) and distal CS (p = 0.0048). There was no difference for sequential or simultaneous pacing. Three patients derived no benefit. CONCLUSIONS: In selected patients, biatrial pacing causes a significant decrease in atrial fibrillation episodes. Optimal lead sites were at the HRA and DCS. Simultaneous pacing conferred no benefit over sequential pacing.     

犬快速肺静脉起搏心房颤动模型中CalpainⅠ在肺静脉肌袖及左心房的表达及意义

目的模拟肺静脉自行发放高频脉冲建立心房颤动的动物模型,研究肺静脉及左心房的CalpainⅠ重构情况,以期阐明CalpainⅠ的变化在持续性房颤的发生和维持中的重要作用。方法30只犬随机分为实验组和对照组,建立犬快速肺静脉起搏持续性心房颤动模型,取组织标本,标本共分4组:①正常犬左心房后壁组;②正常犬左上肺静脉肌袖组;③房颤犬左心房后壁组;④房颤犬左上肺静脉肌袖组。用RT-PCR和W estern印记法分别检测各组的CalpainⅠmRNA和蛋白的表达情况。结果正常犬左心房和肺静脉肌袖的CalpainⅠ的mRNA和蛋白表达水平无明显差异;房颤犬肺静脉和左心房的CalpainⅠ的mRNA和蛋白表达均高于对照组（均P<0.05）,房颤犬肺静脉肌袖CalpainⅠ的mRNA和蛋白表达高于左心房后壁部（均P<0.05）。结论在犬快速肺静脉起博心房颤动模型中,CalpainⅠ肺静脉肌袖和左心房中出现重构,参与了房颤的发生和维持。     

心房颤动犬心房肌肾素-血管紧张素系统改变

目的探讨慢性心房快速起搏诱发心房颤动(房颤)犬心房肌肾素血管紧张素系统(RAS)的改变。方法13只犬随机分为假手术组(n=6)和起搏组(n=7)。起搏组犬无菌开胸后在右心房缝植5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而不起搏。经心外膜电极记录各组犬房颤诱发情况;采用放射免疫方法检测两组犬左心房及右心房组织血管紧张素Ⅰ(AngⅠ)、血管紧张素Ⅱ(AngⅡ)含量及肾素活性;采用逆转录聚合酶链反应(RTPCR)检测两组犬心房肌肾素、血管紧张素原和血管紧张素转换酶mRNA表达水平改变。结果(1)起搏组7只犬均经短阵快速刺激(burstpacing)诱发出房颤,房颤诱发率和平均持续时间较假手术组显著增加(P<0.01);(2)起搏组犬心房肌AngⅠ、AngⅡ含量较假手术组犬心房肌明显升高(P<0.01),肾素活性亦显著增加(P<0.01);同一组犬左心房与右心房组织AngⅠ、AngⅡ含量及肾素活性差异无统计学意义(P>0.05);(3)起搏组犬心房肌肾素、血管紧张素原和血管紧张素转换酶mRNA表达较假手术组犬心房肌显著上调(P<0.01)。结论慢性心房快速起搏诱发房颤犬心房肌AngⅠ、AngⅡ含量及肾素活性显著增加,可能是局部RAS基因表达上调的结果,提示房颤伴随心房肌RAS激活。