局灶性房颤的机制和射频消融治疗研究
摘要
局灶性心房颤动是一种特殊类型的房颤，局灶性房颤发生的关键部位以左房的肺静脉口及入口内1—4mm处发生率最高，占90％以上。正常肺静脉的心肌细胞排列是高度变异的，这种复杂的排列方式和较多的纤维组织可能是肺静脉成为局灶性房颤发生的关键部位的原因。多个研究表明利用射频消融技术治疗房颤是可行的。但目前尚无一种可靠的提示局灶性房颤的临床线索；尚无一种诱发率高重复性好的诱发方案；肺静脉内消融可能导致肺静脉狭窄，使得射频消融治疗房颤存在很大困难。新近研究表明如局灶性房颤的起源部位已确定在肺静脉，可不必再行进一步的标测，而直接将四个(或某个)肺静脉口与左房的其他部分进行电学隔离，从而达到治疗的目的。也有研究表明肺静脉的激动传导常存在时序性。消融最早激动点就能起到治疗作用。我们通过对肺静脉组织结构的进一步研究，分析肺静脉电生理与组织学的联系，探讨局灶性房颤的机制，指导房颤的射频消融治疗。我们的研究发现(1)．犬肺静脉心肌袖的排列方式主要是平行与肺静脉长轴或环肺静脉排列，心肌袖之间有较多的纤维组织；肺静脉的心肌袖多位于肺静脉壁的外侧，心肌袖与肺静脉中层平滑肌细胞被一层纤维组织隔开。上肺静脉的心肌袖厚于下肺静脉；心肌袖的厚度在个研究部位不同，上肺静脉的心肌袖在肺静脉下壁明显较其他时间点厚；下肺静脉的心肌袖在肺静脉上壁明显较其他时间点厚。(2)．在犬的肺静脉－心房交界处心肌细胞的覆盖率是不同的，心肌细胞绝大多数分布于肺静脉的全部周长上，而且在大多数的肺静脉近端心肌纤
第四军医大学博士学位论文
维的排列是无序的c在四个不同的位置上可以标侧到肺静脉电位的比率上肺
静脉高于下肺静脉；肺静脉的电覆盖率均低于心肌细胞的覆盖率。（3）．肺静
脉近端的ERP短于心房的ERP，随刺激频率的加快，肺静脉和心房的ERP均缩
短，但肺静脉的有效不应期仍短于心房。房颤的诱发率在各研究部位不同，
上肺静脉房颤的诱发率明显高于下肺静脉（61％ VS 22％）：房颤持续时间各肺
静脉相比无显著性差异（P＞0．05）。（4）．心房－肺静脉的传导时间在各研究部
位不同，肺静脉到左房的传导时间下肺静脉明显长于上肺静脉（PO．0①。期
前刺激时，犬的肺静脉心肌袖具有心房肌细胞的传导特性。S。到上肺静脉记
录部位（刊的传导时间明显小于到下肺静脉的传导时间（P＜0．0幻，但上肺静
脉记录部位传导时间的变异明显大于下肺静脉（P＜0．05）。（5）．在肺静脉远端
周长上下两个点进行刺激时，最早激动点在钟表盘四个不同位置的分布呈均
态分布。在同一肺静脉不同位置刺激时最早激动点在肺静脉日一致的犬的比
例占20％左右。仰．消融最早激动点后可能出现三种情况①消融最早激动点
后，最早激动点电位消夫，其余各记录点电位及激动顺序未发生变化；②消
融最早激动点后，最早激动点电位消失，其余各记录点电位存在且激动顺序
发生变化。③梢融最早激动点后，最早激动点电位消夫，其余各记录点电位
也消失。（7）．消融上肺静脉所需的点数明显多于下肺静脉（P＜0．05）。消融后，
房颤的诱发率在最早激动点消融组高于环形消融组（60％ VS 14％），房颤持续
时问也是最早激动扒e融组高于环形消融组（V0．帖）。与消融前相比，消融
后即刻的房颤诱发率和房颤持续时间均显著性减少（火0．05）。（幻．我科临床
资料也说明局灶性房颤多起源于双上肺静脉；点消融可以治疗部分局灶性房
颤，但最早激动点消融的效果不如环形消融电隔离；局灶性房颤也可能会引
起心房增大，存在电和解剖的重构。我们得出结论：1．肺静脉的心肌袖的分
布既有共性又有特殊性。上肺静脉的心肌袖厚于下肺静脉：上肺静脉的下部
和下肺静脉的上部心肌袖最厚；肺静脉心肌细胞的排列紊乱，纤维组织较多。
肺静脉具有各向异性传导的组织学基础。2．绝大多数犬的肺静脉近端心肌细
胞覆盖肺静脉的全部周长，在肺静脉周长上可以标侧到肺静脉电位的比率低
3
第四军医大学博士学位论文
干心肌细胞的覆盖率。3．肺静脉的ERP短于心房的ERP，上肺静脉的房颤的诱
发率高于下肺静脉；在各研究点房颤持续时间相比无显著性差异。说明ERP
不是影响房颤的唯一因素。4．肺静脉到左房的传导时间上肺静脉短于下肺静
脉，期前刺激时，肺静脉的传导具有心房肌细胞的传导特性，上肺静脉传导
的变异较大。这可能是局灶性房颤的另一个机制。5．程序刺激可诱发房颤，
肺静脉具有较?
BACKGROUND:Focal atrial fibrillation(FAF) is initiated by the ectopic beats originating within or at the ostium of the pulmonary veins(PV).The structure of the PV is relation with FAF.Radiofrequency ablation(RF) of tissues in PV can eliminate FAF.But the feasibility of this technique is limited by the difficulty in mapping the focus and the incidence of PV narrowing.Circumferential ablation of PV ostium can cure atrial fibrillation.One or two bopoles electrodes showed earliest activation with later and sequential spread to the rest of the venous circumference,Ablation earliest activation site can cure some atrial fibrillation. We study the structure and morphology of PV,To investigate the relationship between structure and morphology and electrophysiology of PV and to provide more information relevant to RF.METHODS: Electrophysiology study was done in 20 structurally normal dogs.First 10 dogs were examined grossly. Histological sections were made from 35 PV. RF was done in latter 10 dogs.RESULTS:(l).The cardial sleeves in SPV were thicker than in IPV(P<0.05). For the SPV, the sleeves were thickest along the inferior walls and thinnest superiorly. The sleeve was composed mainly of circularly or spirally oriented bundles of myocytes.(2).Muscle covered the total PV perimeter and the bundles of cardial cell were disorganise in major of dog. electricty covered only various parts of the perimeter.The percent of perimetric electrical coverage was higher for both SPV than for IPV(P<0.05). (3).ERP of pulmonary vein was significantly shorter than that of left atrium.with the
increasing the frequency of pacing,ERP of pulmonary vein became shorter(P<0.05),but ERP of pulmonary vein was shorter than that of left atrium(P<0.05).Compared with IPV,the percent of atrial fibrillation induced by programmed pacing or Burst pacing was highter in SPV.the duration time of atrial fibrillation was not significantly different.(4).The conduction time from the pacing sites in SPY to left atrium was shorter than that in IPV.During premature stimulation.conductive characterize of atrial muscle was observed in the PV,the heterogeneity of conduction time was significantly bigger in SPY than that in IPV; (5).The earliest PVP was localized to any segment of the perimeter and the site of earliest PVP was not same when pacing was done at the roof,the bottom of PV or sinus rhythm.About 20% dogs, the sites of earliest PVP were same when pacing was done at difference sites;(6).RF deliveried at the earliest activated ostial segment either could elminated the total PVP or only elminated the PVP of the earliest activated site.the sequence of the other sites did chang or not chang.(7).RF total perimeter,the percent of lesion of every pulmonary vein/total lesions was higher in SPV than in IPV(P<0.05).After RKratio and time of induced atrial fibrillation were significantly lower than before RF. But ratio of induced atrial fibrillation was significantly higher in group of the earliest activated site RF, the duration time of atrial fibrillation was longer in group of the earliest activated site RF(P<0.05). (8).Our clinicial data found that 67.0% ectopic beats originated from SPV. the earliest activated site RF could cure some FAF patients,but effect was not better than electrical isolation at PV ostium.FAF could induce atrial enlargement, and electrical and anatomical remodeling.CONCLUSIONS:(l)The cardial sleeves are thicker in SPV than in IPV. For the SPV, the sleeves are thickest along the inferior walls and thinnest superiorly.The myocardial architecture in dog PV is highly variable.The complex arrangement and the spatial relationship between individual cells varies under electron-microscopic
examination and increase in fibrosis may produce greater non-uniform anisotropic properties. (2)ERP of pulmonary vein is shorter than that of left atrium, the percent of atrial fibrillation induced by programmed pacing or Burst pacing is highter in SPV.The short ERP is not only factor of atrial fibrillation.(3)The conduction time from the pacing sites in SPY
第四军医大学博士学位论文
维的排列是无序的c在四个不同的位置上可以标侧到肺静脉电位的比率上肺
静脉高于下肺静脉；肺静脉的电覆盖率均低于心肌细胞的覆盖率。（3）．肺静
脉近端的ERP短于心房的ERP，随刺激频率的加快，肺静脉和心房的ERP均缩
短，但肺静脉的有效不应期仍短于心房。房颤的诱发率在各研究部位不同，
上肺静脉房颤的诱发率明显高于下肺静脉（61％ VS 22％）：房颤持续时间各肺
静脉相比无显著性差异（P＞0．05）。（4）．心房－肺静脉的传导时间在各研究部
位不同，肺静脉到左房的传导时间下肺静脉明显长于上肺静脉（PO．0①。期
前刺激时，犬的肺静脉心肌袖具有心房肌细胞的传导特性。S。到上肺静脉记
录部位（刊的传导时间明显小于到下肺静脉的传导时间（P＜0．0幻，但上肺静
脉记录部位传导时间的变异明显大于下肺静脉（P＜0．05）。（5）．在肺静脉远端
周长上下两个点进行刺激时，最早激动点在钟表盘四个不同位置的分布呈均
态分布。在同一肺静脉不同位置刺激时最早激动点在肺静脉日一致的犬的比
例占20％左右。仰．消融最早激动点后可能出现三种情况①消融最早激动点
后，最早激动点电位消夫，其余各记录点电位及激动顺序未发生变化；②消
融最早激动点后，最早激动点电位消失，其余各记录点电位存在且激动顺序
发生变化。③梢融最早激动点后，最早激动点电位消夫，其余各记录点电位
也消失。（7）．消融上肺静脉所需的点数明显多于下肺静脉（P＜0．05）。消融后，
房颤的诱发率在最早激动点消融组高于环形消融组（60％ VS 14％），房颤持续
时问也是最早激动扒e融组高于环形消融组（V0．帖）。与消融前相比，消融
后即刻的房颤诱发率和房颤持续时间均显著性减少（火0．05）。（幻．我科临床
资料也说明局灶性房颤多起源于双上肺静脉；点消融可以治疗部分局灶性房
颤，但最早激动点消融的效果不如环形消融电隔离；局灶性房颤也可能会引
起心房增大，存在电和解剖的重构。我们得出结论：1．肺静脉的心肌袖的分
布既有共性又有特殊性。上肺静脉的心肌袖厚于下肺静脉：上肺静脉的下部
和下肺静脉的上部心肌袖最厚；肺静脉心肌细胞的排列紊乱，纤维组织较多。
肺静脉具有各向异性传导的组织学基础。2．绝大多数犬的肺静脉近端心肌细
胞覆盖肺静脉的全部周长，在肺静脉周长上可以标侧到肺静脉电位的比率低
3
第四军医大学博士学位论文
干心肌细胞的覆盖率。3．肺静脉的ERP短于心房的ERP，上肺静脉的房颤的诱
发率高于下肺静脉；在各研究点房颤持续时间相比无显著性差异。说明ERP
不是影响房颤的唯一因素。4．肺静脉到左房的传导时间上肺静脉短于下肺静
脉，期前刺激时，肺静脉的传导具有心房肌细胞的传导特性，上肺静脉传导
的变异较大。这可能是局灶性房颤的另一个机制。5．程序刺激可诱发房颤，
肺静脉具有较?
BACKGROUND:Focal atrial fibrillation(FAF) is initiated by the ectopic beats originating within or at the ostium of the pulmonary veins(PV).The structure of the PV is relation with FAF.Radiofrequency ablation(RF) of tissues in PV can eliminate FAF.But the feasibility of this technique is limited by the difficulty in mapping the focus and the incidence of PV narrowing.Circumferential ablation of PV ostium can cure atrial fibrillation.One or two bopoles electrodes showed earliest activation with later and sequential spread to the rest of the venous circumference,Ablation earliest activation site can cure some atrial fibrillation. We study the structure and morphology of PV,To investigate the relationship between structure and morphology and electrophysiology of PV and to provide more information relevant to RF.METHODS: Electrophysiology study was done in 20 structurally normal dogs.First 10 dogs were examined grossly. Histological sections were made from 35 PV. RF was done in latter 10 dogs.RESULTS:(l).The cardial sleeves in SPV were thicker than in IPV(P<0.05). For the SPV, the sleeves were thickest along the inferior walls and thinnest superiorly. The sleeve was composed mainly of circularly or spirally oriented bundles of myocytes.(2).Muscle covered the total PV perimeter and the bundles of cardial cell were disorganise in major of dog. electricty covered only various parts of the perimeter.The percent of perimetric electrical coverage was higher for both SPV than for IPV(P<0.05). (3).ERP of pulmonary vein was significantly shorter than that of left atrium.with the
increasing the frequency of pacing,ERP of pulmonary vein became shorter(P<0.05),but ERP of pulmonary vein was shorter than that of left atrium(P<0.05).Compared with IPV,the percent of atrial fibrillation induced by programmed pacing or Burst pacing was highter in SPV.the duration time of atrial fibrillation was not significantly different.(4).The conduction time from the pacing sites in SPY to left atrium was shorter than that in IPV.During premature stimulation.conductive characterize of atrial muscle was observed in the PV,the heterogeneity of conduction time was significantly bigger in SPY than that in IPV; (5).The earliest PVP was localized to any segment of the perimeter and the site of earliest PVP was not same when pacing was done at the roof,the bottom of PV or sinus rhythm.About 20% dogs, the sites of earliest PVP were same when pacing was done at difference sites;(6).RF deliveried at the earliest activated ostial segment either could elminated the total PVP or only elminated the PVP of the earliest activated site.the sequence of the other sites did chang or not chang.(7).RF total perimeter,the percent of lesion of every pulmonary vein/total lesions was higher in SPV than in IPV(P<0.05).After RKratio and time of induced atrial fibrillation were significantly lower than before RF. But ratio of induced atrial fibrillation was significantly higher in group of the earliest activated site RF, the duration time of atrial fibrillation was longer in group of the earliest activated site RF(P<0.05). (8).Our clinicial data found that 67.0% ectopic beats originated from SPV. the earliest activated site RF could cure some FAF patients,but effect was not better than electrical isolation at PV ostium.FAF could induce atrial enlargement, and electrical and anatomical remodeling.CONCLUSIONS:(l)The cardial sleeves are thicker in SPV than in IPV. For the SPV, the sleeves are thickest along the inferior walls and thinnest superiorly.The myocardial architecture in dog PV is highly variable.The complex arrangement and the spatial relationship between individual cells varies under electron-microscopic
examination and increase in fibrosis may produce greater non-uniform anisotropic properties. (2)ERP of pulmonary vein is shorter than that of left atrium, the percent of atrial fibrillation induced by programmed pacing or Burst pacing is highter in SPV.The short ERP is not only factor of atrial fibrillation.(3)The conduction time from the pacing sites in SPY
引文
1． Haissaguerre M.Jais P,Shah DC,et al.Right and left atrial radiofrequency catheter therapy of paroxysmal atrial fibrillation.J Cardiovasc Electrophysiol, 1996,7:1132
2． Jais P,Haissaguerre M,Shah DC,et al.A focal source of atrial fibrillation treated by discrete radiofrequency ablation.Circulation, 1997,95:572-576
3． Haissaguerre MJais P,Shah DC.et al.Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins .N Engl J Med,1998,339:659-666
4． Hocini M.Haissaguerre M.Jais P.et al.Predominant origin of ectopic triggering atrial fibrillation from the pulmonary veins .'mapping and ablation in 100 patients.PACE,1999,22(ptⅡ):A75
5． Chen SA,Tai CT,Yu WC,et al.Right atrial focal atrial fibrillation:electrophysiologic characteristics and radiofrequency catheter ablation.J Cardiovasc Electrophysiol, 1999,10:328
6． Hsieh MH,Chen SA,Tai CT,et al.Double multielectrode mapping catheters facilitate radiofrequency catheter ablation of focal atrial fibrillation originating from pulmonary veins.J Cardiovasc Electrophysiol,1999,10:136
7． Nathan H,Eliakim M.The junction between the left atrium and the pulmonary veins :an anatomic study of human hearts.Circulation, 1996,34:412
8． Chen SA.Hsieh MH,Tai CT.et al.Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins:Electrophysiologic characteristics,pharmacologic responses.and radiofrequency catheter ablation.Circulation, 1999． 100:1879-1886
9． Ho SY,Cabrera JA.Tran VH,et al.Architecture of the pulmonary-veins :Relevance to radiofrequency ablation.Heart,2001,86:265
10． De Ruiter MC,Gittenberger-Ge Groot AC,Wenink ACG,et al.In normal development pulmonary veins are connected to the sinus venous segment in the left atrium.Anat Rec,1995,243:84-92
11． Webb S,Brown NA,Wessels A,et al.Development of the murine pulmonary vein and its relationship to the embryonic venous sinus.Anat Rec,1998,250:325-334
12． Masani F.Node-like cells in the myocardial layer of the pulmonary vein of rats:an ultra structure study.J Anat.1986,145:133-142
13． Cheung DW.Electrical activity of the pulmonary vein and its interaction with
the right atrium in the guinea-pig.J Physiol,1980;314:445-456
14． Blom NA,Gittenberger-de Groot AC.Deruiter MC,et al.Development of the cardiac conduction tissue in human embryos using HNK-I antigen expression:possible relevance for understanding of abnormal atrial automaticity.Circulation,1999,99:800-806
15． Cheung DW.Pulmonary vein as an ectopic focus in digitalis-induced arrhythmia.Nature,1981 ,294:582
16． Nam GB,Choi KJ,Leem CH,et al.The characteristics of spontaneous action potentials of myocytes in rabbit pulmonary veins:Implication in intiation mechanism of focal atrial fibrillation. PACE. 23(part Ⅱ ):604
17． 马长生，杨延宗，刘旭，等.阵发性心房颤动局灶性消融治疗的方法学.中国心 脏起搏与心电生理杂志，2000；1：57
18． Haissaguerre M,Shah DC,Jans P,et al.Electrophysiologyical breakthroughs from the left atrium to the pulmonary veins. Circulation,2000, 102:2463
19． Chen YJ,Chen SA,Lin CI.Conduction block protects atrium from the arrhythmogenic activity of the pulmonary veins.PACE,23(part Ⅱ ):616
20． Vincent Deen,Jitendra Vohra,Jonathan Kalman.et al. Characteristic P wave morphology during vein pacing.PACE,1999;22(pt Ⅱ ):771
21． Vincent Deen,Jitendra Vohra, Jonathan Kalman.et al. Pulmonary vein paced activation sequence mapping:Comparison with activation sequence during onset of focal atrial fibrillation.PACE.1999(pt Ⅱ ):797
22． Ponti RD, Salerno JA,Zardini M.et al. Site-dependence of A-P interval and P-wave duration in patients with focal atrial tachycardia.PACE,1999;22(pt Ⅱ):889
23． Hsieh MH,Tai CT,Tsai CF,et al. Pulmonary vein electrogram characteristics in patients with focal sources of paroxysmal atrial fibrillation.J Cardiovasc Electrophysiol,2000; 11 (9) :953
24． Gardner E.O Rahilly R.The nen'e supply and conducting system of the human heart at the end of the embryonic period proper. J Anat,1976;121:571
25． Tsai CF; Chen SA; Tai CT;et al. Bezold-Jarisch-like reflex during radiofrequency ablation of the pulmonary vein tissues in patients with paroxysmal focal atrial fibrillation. J Cardiovasc Electrophysiol. 1999; 10(1) : 27-35
26． Tai CT.Chiou CW.Hsieh MH.et al. Effect of phenylephrine on focal atrial fibrillation originating in the pulmonary veins and superior vena cava. J Am
Coll Cardiol,2000;36:788
27． Schauerte PN,Scherlag BJ,Scherlag MA,et al.Atrial fibrillation initiated by ectopic beats originating in the pulmonary veins and superior vena cava: reproducible induction by cardiac autonomic nerve stimulation. PACE,1999;4(part Ⅱ):768
28． Lee KH,Wen ZC,Hsieh MH,et al.Changes of autonomic function before initiation of paroxysmal atrial fibrillation by ectopic beats from pulmonary veins. PACE,2000;4(part Ⅱ):607
29． Hsieh MH,Tai CT.Tsai CF,et al.Pulmonary vein electrogram characteristics in patients with focal sources of paroxysmal atrial fibrillation.J Cardiovasc Electrophysiol.2000;11(9) :954
30． Haissaguerre M,Shah DC,Jais P,et al.P on T extrasystoles are highly predictive of a pulmonary vein origin.PACE,1999;22(pt Ⅱ ):836
31． Jing TP,Yamane T,Shah DC,et al.An algorithm for identification of PV origin of pacing from P wave morphology.PACE,2000;23(pt Ⅱ ):556
32． Groenewegen AS,Mlynash MD,Guerra PG,et al. Atlas of paced body sueface P wave integral maps for localization of focal left atrial arrhythmia.PACE,2000;23(pt Ⅱ ):556
33． Gerstenfeld EP. Groenewegen AS,Lux RL,et al.An optimal electrode set for localizing atrial activation originating from the pulmonary veins. PACE,2000;23(ptⅡ):583
34． Hwang C,Karagueuzian HS,Chen PS.Idiopathie paroxysmal atrial fibrillation induced by a focal discharge mechanism in the left superior pulmonary vein:possible roles of the ligament of Marshall. J Cardiovasc Electrophysiol. 1999:10(6) :636
35． Ashar MS,Pennington JC,Nayak H,et al.Localization of arrhythmogenic triggers of atrial fibrillation. J Cardiovasc Electrophysiol,2000; 11(12) : 1300
36． Yasuda T,Kumagai K.Tojo H,et al.Activation of right atrium mapping predicts the pulmonary vein origin of atrial fibrillation.PACE,2000;23(pt Ⅱ )698
37． Lee SH,Tai CT,Lin WS,et al.Predicting the arrhythmogenic foci of atrial fibrillation before atrial transseptal procedure:implication for catheter ablation.J Cardiovasc Electrophysiol,2000;11(7) :750
38． Haissaguerre M.Jais RShah DC,et al.Plurifocal sources of atrial fibrillation initiation from the pulmonary veins.PACE,1999,22(ptⅡ ):707
39． Jais P.Shah DC.Hocini M.et al.Radiofrequency catheter ablation for atrial
fibrillation. J Cardiovasc Electrophysiol,2000;11(7) :759
40． Tes HF,Lau CRKou W.et al.Comparison of endocardial activation tims at effective and ineffective ablation sites within the pulmonary veins.J Cardiovasc Electrophysiol,2000; 11 (2) : 155
41． Schneider MAE,Ndrepepa G,Zrenner B,et al.Noncontact mapping-guided catheter ablation of atrial fibrillation associated with left atrial ectopy. J Cardiovasc Electrophysiol,2000;11:475
42． Friedman PA,Grice S,Munger TM.et al.Spot welding the trigger in focal atrial fibrillation ablation. J Cardiovasc Electrophysiol,2000; 11:1061
43． Moe GK.On the multiple wavelet hypothesis of atrial fibrillation.Arch Int Pharmacodyn Ther.l962,140:183-188
44． Cox JL,Boineau JP,Schuessler RB.et al.Five year experience with the maze procedure for atrial fibrillation.Ann Thorac Surg.1993,56:814-823
45． Takahashi A,Jais P,Shah DC,et al.Successful focal ablation of ectopy reinitiating persistent atrial fibrillation.PACE,1999,22(pt Ⅱ):905
46． Haissaguerre M,Jais P,Shah DC,et al.Successful focal catheter ablation of chronic atrial fibrillation.PACE,1999,22(pt Ⅱ ):A26
47． Haissaguerre M.Marcus FI,Fischer B,et al.Radiofrequency catheter ablation in unusual mechanisms of atrial fibrillation:Report of three cases.J Cardiovasc Electrophysiol, 1994,5:743
48． Shah DC,Haissaguerre M,Jais P,et al.Provocative manoeuvers for inducing pulmonary vein ectopy.PACE,1999,22(pt Ⅱ ):738
49． Hsieh MH,Tai CT.Tsai CF,et al.An algorithm for facilitating spontaneous initiation of pulmonary vein-dependent focal atrial fibrillation.PACE,1999,22(pt Ⅱ ):A76
50． Sra J,Biehl M.Blanck Z,et al.Spontaneous re-initiation of atrial fibrillation following transvenous atrial defibrillation.PACE, 1998,21:1105
51． Lau CP,Tse HF,Ayers GM.Defibrillation-guided radiofrequency ablation of atrial fibrillation secondary to an atrial focus.J Am Coll Cardiol, 1999,33:1217
52． Schwartzman D.Predis L.Simultaneous multielectrode microcatheter mapping of the pulmonary veins in patients with paroxysmal atrial fibrillation.PACE.1999,22(ptⅡ):710
53． Wijffels MC,Kirchhof CJ,Dorland R,et al.Atrial fibrillation begets atrial fibrillations study in awake chronically instrumented goats.Circulation.1995． 92:1954
54． Vergara I,Martin D.Bahnson T.et al.Clinical predictors of successful focal atrial fibrillation ablation.PACE,1999,22(pt Ⅱ):772
55． Robbins IM,Colvin EV,Doyle TP,et al.Pulmonary vein stenosis after catheter ablation of atrial fibrillation.Circulation,1998,98:1769
56． Jais P,Shah DC,Haissaguerre M,et al.Pulmonary vein patency after radiofrequency ablation.PACE,1999,22(pt Ⅱ ):738
57． Chen SA,Hsieh MH,Tai CT.et al.Does early recurrence of focal atrial fibrillation after successful catheter ablation of triggering ectopic foci need reqeated ablation immediately?PACE,1999,22(pt Ⅱ):865
58． Arentz T,Ott P,Rosenthal J,et al.Paroxysmal atrial fibrillation of focal origin:high recurrence rate after initial successful catheter ablation.PACE,1999． 22(pt Ⅱ ):843
59． Swartz J,Hassett J.Bednared M.et al.Single burn pulmonary vein isolation with a virtual circumferential electrode.PACE,1998,21(pt Ⅱ):803
60． Fieguth HG,Wahlers T,Borst HG.Inhibition of atrial fibrillation by pulmonary vein isolation and auricular resection experimental study in a sheep model.Eur J Cardiothoracic Surg, 1997,11:714
61． Kottkamp H,Hindricks G,Hammel D,et al.Intraoperative radiofrequency ablation of chronic atrial fibrillations left atrial curative approach by elimination of anatomic "anchor" reentrant circuits.J Cardiovasc Electrophysiol, 1999,10:772
62． Guerra PG,Lesh MD.The role of nonpharmacologic therapies for the treatment of atrial fibrillation.J Cardiovasc Electrophysiol, 1999,10:450
63． Pappone C,Rosanio S,Oreto R,et al.Circumferential radiofrequency ablatiob of pulmonary vein ostia:A new anatomic approach for curing atrial fibrillation.Circulation.2000． 102:2619
2． Jais P,Haissaguerre M,Shah DC,et al.A focal source of atrial fibrillation treated by discrete radiofrequency ablation.Circulation, 1997,95:572-576
3． Haissaguerre MJais P,Shah DC.et al.Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins .N Engl J Med,1998,339:659-666
4． Hocini M.Haissaguerre M.Jais P.et al.Predominant origin of ectopic triggering atrial fibrillation from the pulmonary veins .'mapping and ablation in 100 patients.PACE,1999,22(ptⅡ):A75
5． Chen SA,Tai CT,Yu WC,et al.Right atrial focal atrial fibrillation:electrophysiologic characteristics and radiofrequency catheter ablation.J Cardiovasc Electrophysiol, 1999,10:328
6． Hsieh MH,Chen SA,Tai CT,et al.Double multielectrode mapping catheters facilitate radiofrequency catheter ablation of focal atrial fibrillation originating from pulmonary veins.J Cardiovasc Electrophysiol,1999,10:136
7． Nathan H,Eliakim M.The junction between the left atrium and the pulmonary veins :an anatomic study of human hearts.Circulation, 1996,34:412
8． Chen SA.Hsieh MH,Tai CT.et al.Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins:Electrophysiologic characteristics,pharmacologic responses.and radiofrequency catheter ablation.Circulation, 1999． 100:1879-1886
9． Ho SY,Cabrera JA.Tran VH,et al.Architecture of the pulmonary-veins :Relevance to radiofrequency ablation.Heart,2001,86:265
10． De Ruiter MC,Gittenberger-Ge Groot AC,Wenink ACG,et al.In normal development pulmonary veins are connected to the sinus venous segment in the left atrium.Anat Rec,1995,243:84-92
11． Webb S,Brown NA,Wessels A,et al.Development of the murine pulmonary vein and its relationship to the embryonic venous sinus.Anat Rec,1998,250:325-334
12． Masani F.Node-like cells in the myocardial layer of the pulmonary vein of rats:an ultra structure study.J Anat.1986,145:133-142
13． Cheung DW.Electrical activity of the pulmonary vein and its interaction with
the right atrium in the guinea-pig.J Physiol,1980;314:445-456
14． Blom NA,Gittenberger-de Groot AC.Deruiter MC,et al.Development of the cardiac conduction tissue in human embryos using HNK-I antigen expression:possible relevance for understanding of abnormal atrial automaticity.Circulation,1999,99:800-806
15． Cheung DW.Pulmonary vein as an ectopic focus in digitalis-induced arrhythmia.Nature,1981 ,294:582
16． Nam GB,Choi KJ,Leem CH,et al.The characteristics of spontaneous action potentials of myocytes in rabbit pulmonary veins:Implication in intiation mechanism of focal atrial fibrillation. PACE. 23(part Ⅱ ):604
17． 马长生，杨延宗，刘旭，等.阵发性心房颤动局灶性消融治疗的方法学.中国心 脏起搏与心电生理杂志，2000；1：57
18． Haissaguerre M,Shah DC,Jans P,et al.Electrophysiologyical breakthroughs from the left atrium to the pulmonary veins. Circulation,2000, 102:2463
19． Chen YJ,Chen SA,Lin CI.Conduction block protects atrium from the arrhythmogenic activity of the pulmonary veins.PACE,23(part Ⅱ ):616
20． Vincent Deen,Jitendra Vohra,Jonathan Kalman.et al. Characteristic P wave morphology during vein pacing.PACE,1999;22(pt Ⅱ ):771
21． Vincent Deen,Jitendra Vohra, Jonathan Kalman.et al. Pulmonary vein paced activation sequence mapping:Comparison with activation sequence during onset of focal atrial fibrillation.PACE.1999(pt Ⅱ ):797
22． Ponti RD, Salerno JA,Zardini M.et al. Site-dependence of A-P interval and P-wave duration in patients with focal atrial tachycardia.PACE,1999;22(pt Ⅱ):889
23． Hsieh MH,Tai CT,Tsai CF,et al. Pulmonary vein electrogram characteristics in patients with focal sources of paroxysmal atrial fibrillation.J Cardiovasc Electrophysiol,2000; 11 (9) :953
24． Gardner E.O Rahilly R.The nen'e supply and conducting system of the human heart at the end of the embryonic period proper. J Anat,1976;121:571
25． Tsai CF; Chen SA; Tai CT;et al. Bezold-Jarisch-like reflex during radiofrequency ablation of the pulmonary vein tissues in patients with paroxysmal focal atrial fibrillation. J Cardiovasc Electrophysiol. 1999; 10(1) : 27-35
26． Tai CT.Chiou CW.Hsieh MH.et al. Effect of phenylephrine on focal atrial fibrillation originating in the pulmonary veins and superior vena cava. J Am
Coll Cardiol,2000;36:788
27． Schauerte PN,Scherlag BJ,Scherlag MA,et al.Atrial fibrillation initiated by ectopic beats originating in the pulmonary veins and superior vena cava: reproducible induction by cardiac autonomic nerve stimulation. PACE,1999;4(part Ⅱ):768
28． Lee KH,Wen ZC,Hsieh MH,et al.Changes of autonomic function before initiation of paroxysmal atrial fibrillation by ectopic beats from pulmonary veins. PACE,2000;4(part Ⅱ):607
29． Hsieh MH,Tai CT.Tsai CF,et al.Pulmonary vein electrogram characteristics in patients with focal sources of paroxysmal atrial fibrillation.J Cardiovasc Electrophysiol.2000;11(9) :954
30． Haissaguerre M,Shah DC,Jais P,et al.P on T extrasystoles are highly predictive of a pulmonary vein origin.PACE,1999;22(pt Ⅱ ):836
31． Jing TP,Yamane T,Shah DC,et al.An algorithm for identification of PV origin of pacing from P wave morphology.PACE,2000;23(pt Ⅱ ):556
32． Groenewegen AS,Mlynash MD,Guerra PG,et al. Atlas of paced body sueface P wave integral maps for localization of focal left atrial arrhythmia.PACE,2000;23(pt Ⅱ ):556
33． Gerstenfeld EP. Groenewegen AS,Lux RL,et al.An optimal electrode set for localizing atrial activation originating from the pulmonary veins. PACE,2000;23(ptⅡ):583
34． Hwang C,Karagueuzian HS,Chen PS.Idiopathie paroxysmal atrial fibrillation induced by a focal discharge mechanism in the left superior pulmonary vein:possible roles of the ligament of Marshall. J Cardiovasc Electrophysiol. 1999:10(6) :636
35． Ashar MS,Pennington JC,Nayak H,et al.Localization of arrhythmogenic triggers of atrial fibrillation. J Cardiovasc Electrophysiol,2000; 11(12) : 1300
36． Yasuda T,Kumagai K.Tojo H,et al.Activation of right atrium mapping predicts the pulmonary vein origin of atrial fibrillation.PACE,2000;23(pt Ⅱ )698
37． Lee SH,Tai CT,Lin WS,et al.Predicting the arrhythmogenic foci of atrial fibrillation before atrial transseptal procedure:implication for catheter ablation.J Cardiovasc Electrophysiol,2000;11(7) :750
38． Haissaguerre M.Jais RShah DC,et al.Plurifocal sources of atrial fibrillation initiation from the pulmonary veins.PACE,1999,22(ptⅡ ):707
39． Jais P.Shah DC.Hocini M.et al.Radiofrequency catheter ablation for atrial
fibrillation. J Cardiovasc Electrophysiol,2000;11(7) :759
40． Tes HF,Lau CRKou W.et al.Comparison of endocardial activation tims at effective and ineffective ablation sites within the pulmonary veins.J Cardiovasc Electrophysiol,2000; 11 (2) : 155
41． Schneider MAE,Ndrepepa G,Zrenner B,et al.Noncontact mapping-guided catheter ablation of atrial fibrillation associated with left atrial ectopy. J Cardiovasc Electrophysiol,2000;11:475
42． Friedman PA,Grice S,Munger TM.et al.Spot welding the trigger in focal atrial fibrillation ablation. J Cardiovasc Electrophysiol,2000; 11:1061
43． Moe GK.On the multiple wavelet hypothesis of atrial fibrillation.Arch Int Pharmacodyn Ther.l962,140:183-188
44． Cox JL,Boineau JP,Schuessler RB.et al.Five year experience with the maze procedure for atrial fibrillation.Ann Thorac Surg.1993,56:814-823
45． Takahashi A,Jais P,Shah DC,et al.Successful focal ablation of ectopy reinitiating persistent atrial fibrillation.PACE,1999,22(pt Ⅱ):905
46． Haissaguerre M,Jais P,Shah DC,et al.Successful focal catheter ablation of chronic atrial fibrillation.PACE,1999,22(pt Ⅱ ):A26
47． Haissaguerre M.Marcus FI,Fischer B,et al.Radiofrequency catheter ablation in unusual mechanisms of atrial fibrillation:Report of three cases.J Cardiovasc Electrophysiol, 1994,5:743
48． Shah DC,Haissaguerre M,Jais P,et al.Provocative manoeuvers for inducing pulmonary vein ectopy.PACE,1999,22(pt Ⅱ ):738
49． Hsieh MH,Tai CT.Tsai CF,et al.An algorithm for facilitating spontaneous initiation of pulmonary vein-dependent focal atrial fibrillation.PACE,1999,22(pt Ⅱ ):A76
50． Sra J,Biehl M.Blanck Z,et al.Spontaneous re-initiation of atrial fibrillation following transvenous atrial defibrillation.PACE, 1998,21:1105
51． Lau CP,Tse HF,Ayers GM.Defibrillation-guided radiofrequency ablation of atrial fibrillation secondary to an atrial focus.J Am Coll Cardiol, 1999,33:1217
52． Schwartzman D.Predis L.Simultaneous multielectrode microcatheter mapping of the pulmonary veins in patients with paroxysmal atrial fibrillation.PACE.1999,22(ptⅡ):710
53． Wijffels MC,Kirchhof CJ,Dorland R,et al.Atrial fibrillation begets atrial fibrillations study in awake chronically instrumented goats.Circulation.1995． 92:1954
54． Vergara I,Martin D.Bahnson T.et al.Clinical predictors of successful focal atrial fibrillation ablation.PACE,1999,22(pt Ⅱ):772
55． Robbins IM,Colvin EV,Doyle TP,et al.Pulmonary vein stenosis after catheter ablation of atrial fibrillation.Circulation,1998,98:1769
56． Jais P,Shah DC,Haissaguerre M,et al.Pulmonary vein patency after radiofrequency ablation.PACE,1999,22(pt Ⅱ ):738
57． Chen SA,Hsieh MH,Tai CT.et al.Does early recurrence of focal atrial fibrillation after successful catheter ablation of triggering ectopic foci need reqeated ablation immediately?PACE,1999,22(pt Ⅱ):865
58． Arentz T,Ott P,Rosenthal J,et al.Paroxysmal atrial fibrillation of focal origin:high recurrence rate after initial successful catheter ablation.PACE,1999． 22(pt Ⅱ ):843
59． Swartz J,Hassett J.Bednared M.et al.Single burn pulmonary vein isolation with a virtual circumferential electrode.PACE,1998,21(pt Ⅱ):803
60． Fieguth HG,Wahlers T,Borst HG.Inhibition of atrial fibrillation by pulmonary vein isolation and auricular resection experimental study in a sheep model.Eur J Cardiothoracic Surg, 1997,11:714
61． Kottkamp H,Hindricks G,Hammel D,et al.Intraoperative radiofrequency ablation of chronic atrial fibrillations left atrial curative approach by elimination of anatomic "anchor" reentrant circuits.J Cardiovasc Electrophysiol, 1999,10:772
62． Guerra PG,Lesh MD.The role of nonpharmacologic therapies for the treatment of atrial fibrillation.J Cardiovasc Electrophysiol, 1999,10:450
63． Pappone C,Rosanio S,Oreto R,et al.Circumferential radiofrequency ablatiob of pulmonary vein ostia:A new anatomic approach for curing atrial fibrillation.Circulation.2000． 102:2619