房室结折返性心动过速与冠状窦及后延伸连接蛋白43表达的关系
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摘要
目的:选取兔后延伸及冠状窦作为研究对象,利用组织形态学和分子学探讨房室结折返性心动过速(AVNRT)可能的发生机制。
方法:通过心电生理检查将20只新西兰大白兔分为双径路组和无双径路组,前者在给予电生理刺激(包括心房递增刺激、心房和心室的程控期前刺激)的过程中出现跳跃现象、心房/心室双重反应、或能诱发出房室结折返性心动过速,后者则不能。剪取含有Koch三角及冠状静脉窦的组织标本,自冠状窦口约1 mm处将标本分为两部分,Koch三角标本采取冠状切便于观察后延伸,冠状窦标本矢状切,常规做H-E染色。同时对标本冠状静脉窦及后延伸进行连接蛋白43的免疫组化染色,并应用Ipp6.0进行平均光密度半定量分析,最后运用SPSS 11.0统计软件分析对比。
结果:
1.电生理刺激结果
20只新西兰大白兔经过右心房、右心室递增刺激及程序刺激有5只诱发出折返性心动过速,其中1只明显存在跳跃现象,1只观察到心室双重反应。双径路组Koch三角大小与心动过速周期及程序刺激时最大AV间期无相关关系
2.光学显微镜结果
冠状窦周围均存在肌袖细胞,随着肌袖纤维向远端延伸,肌袖纤维分布逐渐疏松,甚至呈小岛状分布于纤维或脂肪组织之间。致密结由2层细胞组成,致密结向后即向冠状窦口连续切片可见后延伸,所有标本均可见后延伸,其中20只标本可见右后延伸,3只标本可观察到左后延伸,后延伸的细胞排列与致密结相比稀疏。
3.免疫组化结果
连接蛋白在房室结深层细胞表达阴性,浅层细胞及中层细胞呈弱阳性。两组标本后延伸连接蛋白43表达均为阴性,Cx43在CS肌袖细胞胞膜呈阳性表达。双径路组冠状窦连接蛋白43表达强于左心房,非双径路组冠状窦与左心房连接蛋白表达未见差异。
结论:
1.慢径传导与Koch三角大小无明确关系,是以其特有的组织结构为基础的。
2.冠状窦肌袖自左房斜行走行至冠状窦,在冠状窦口与右心房组织相连,作为左右心房间的电传导通路,参与了房室结折返性心动过速。
3.左后延伸及右后延伸均具有结样细胞特性,具有慢径传导的组织学基础,不同比例的存在于正常房室交界区,当传导速度和不应期改变时,显示出双径的特性,致密结的浅表组过渡细胞群在连接致密结与结前心房肌,深层组过渡细胞群连接致密结深部与左侧房间隔,作为快通路传导纤维使快径逆传具有多种出口。
4.连接蛋白43在房室结深层细胞表达阴性,而浅层细胞及中层细胞呈弱阳性可以帮助解释双重输入和或纵行分离,窦房结的冲动经心房组织传到房室结前上方的浅层细胞到达房室束,而适时的期前收缩由于不应期的影响在快径受阻,冲动沿界嵴在冠状窦口下缘传导至后延伸,后延伸具有结样细胞特性且连接蛋白43表达阴性,具有慢径传导的组织学及分子学基础,而后经致密结深层到达房室束,在结的后方可有电传导的出口,快慢径间由于传导速度不同导致纵向分离,为折返环的形成奠定了基础。双径路组冠状静脉窦与周围心房组织连接蛋白表达的差异造成传导速度不同,有可能为左、右心房电传导过程中形成折返奠定了结构基础。冠状窦Cx43表达的差异造成快径路逆向传导障碍可能是室上速诱发的限制因素。
综上所述,房室结存在多丛折返的组织学基础,而临床可表现为多种复杂的电生理现象,这为临床中常规消融未能成功的患者,在二尖瓣环的后侧及冠状窦内成功消融提供了理论依据。
Objective: To study the possible mechanism of atrioventricular nodal reentrant tachycardia by observing and detecting the morphology characteristic and Cx43 expression in coronary sinus and posterior extension .
Method: 20 New Zealand rabbits were divided into two groups by electro-physiological examination: dual-pathway group and non-dual-pathway group. In the former group, jump phenomenon or atrium / ventricle double reaction or atrioventricular nodal reentrant tachycardia was found out during electro-physiological stimulus, nor the later group. Then the preparation Includes coronary sinus and Koch's triangle was cut out and devided into two parts since 1mm from the coronary sinus ostium(CSO). Coronal sections apply to Koch's triangle in order to observe the morphology of PNE . The rest preparation was sliced by Sagittal plane. To observe Cx43 by H-E and immunohistochemistry of posterior extension and coronary sinus.Ipp6.0 was used to analysis quantitatively Cx43 expression ,then statistical analysis data by SPSS11.0 software .
Results:
1 .Electro-physiological stimulus:
Atrioventricular nodal reentrant tachycardial was induced in 5 rabbits during electro-physiological stimulus. There are 1 rabbit with jump phenomenon and 1 rabbit with ventricle double reaction were found out in 2 rabbits; There is no correlation between the size of Koch's triangle and the AV interval and the cycle of tachcardia in dual-pathway group.
2.Morphology:
(1) Coronary sinus was surrounded by myocardial coat, which become thin from CSO toward distal, even was covered only by epicardical fat or fibers. Compact node was consisted of two layers cell bundle. PNE was found by serial sections from compact node that is deep layer cells of AVN to CSO in all specimens. Three specimens have left posterior extension. Right posterior extension can be seen in all specimens. Cells in PNE were sparser compared with compact node.
3. Immunohistochemistry:
Cx43 express negative in deep atrioventricular node cells, weakly positive in superficial and intermediate cells. Cx43 express negative in posterior extention in both groups. coronary sinus myocardial coat Cx43 Positive expression in membrane. In dual-pathway group, coronary sinus expression of Cx43 are higher than left atrium. Non-dual-pathway group had no significant difference
Conclusion:
1. conduction of slow pathway has special structure rather than base on size of Koch's triangle.
2. Coronary sinus connect left atrium and right atrium by myocardial coat,which involve in reentrant cycle.
3. Compact node and posterior extension have characteristic of slow pathway. Dual A-V nodal pathways display when conduction of velocity or refractory changed. Due to there are more than one fast pathway, impulse propagation not only from deep layer of transitional cells to left atrial septum ,then reach to right atrium via of coronary sinus,but also from superficial layer of transitional cells to the top of Koch's triangle.
4. Cx43 negative express in deep atrioventricular node cells, weakly positive express in superficial and intermediate cells can explain longitudinal dissociation. Sinus impulse propagation from atrium to Superficial layer and middle layer cell bud dle ,then reach to His bundle. Premature systole block in the fastway because of refractory .The activation conduct from inferior margin of CSO to PNE, which have charateristics of nodal cells and express Cx43 negatively. After successful ablation of right posterior extension, the charateristics of slow conduction display in left posterior extension. Difference in morphology of coronary sinus and difference in expression of Cx43 maybe the pathology mechanism of AVNRT. We consider the block of reverse transmission is limiting factor of atrioventricular nodal reentranttachycardia.
Multiple phenomenon of electrophysiology seems easy to understand according to this view. The study on the possible mechanism of AVNRT can provide theoretical evidence for radiofrequency catheter ablation on different focal.
方法:通过心电生理检查将20只新西兰大白兔分为双径路组和无双径路组,前者在给予电生理刺激(包括心房递增刺激、心房和心室的程控期前刺激)的过程中出现跳跃现象、心房/心室双重反应、或能诱发出房室结折返性心动过速,后者则不能。剪取含有Koch三角及冠状静脉窦的组织标本,自冠状窦口约1 mm处将标本分为两部分,Koch三角标本采取冠状切便于观察后延伸,冠状窦标本矢状切,常规做H-E染色。同时对标本冠状静脉窦及后延伸进行连接蛋白43的免疫组化染色,并应用Ipp6.0进行平均光密度半定量分析,最后运用SPSS 11.0统计软件分析对比。
结果:
1.电生理刺激结果
20只新西兰大白兔经过右心房、右心室递增刺激及程序刺激有5只诱发出折返性心动过速,其中1只明显存在跳跃现象,1只观察到心室双重反应。双径路组Koch三角大小与心动过速周期及程序刺激时最大AV间期无相关关系
2.光学显微镜结果
冠状窦周围均存在肌袖细胞,随着肌袖纤维向远端延伸,肌袖纤维分布逐渐疏松,甚至呈小岛状分布于纤维或脂肪组织之间。致密结由2层细胞组成,致密结向后即向冠状窦口连续切片可见后延伸,所有标本均可见后延伸,其中20只标本可见右后延伸,3只标本可观察到左后延伸,后延伸的细胞排列与致密结相比稀疏。
3.免疫组化结果
连接蛋白在房室结深层细胞表达阴性,浅层细胞及中层细胞呈弱阳性。两组标本后延伸连接蛋白43表达均为阴性,Cx43在CS肌袖细胞胞膜呈阳性表达。双径路组冠状窦连接蛋白43表达强于左心房,非双径路组冠状窦与左心房连接蛋白表达未见差异。
结论:
1.慢径传导与Koch三角大小无明确关系,是以其特有的组织结构为基础的。
2.冠状窦肌袖自左房斜行走行至冠状窦,在冠状窦口与右心房组织相连,作为左右心房间的电传导通路,参与了房室结折返性心动过速。
3.左后延伸及右后延伸均具有结样细胞特性,具有慢径传导的组织学基础,不同比例的存在于正常房室交界区,当传导速度和不应期改变时,显示出双径的特性,致密结的浅表组过渡细胞群在连接致密结与结前心房肌,深层组过渡细胞群连接致密结深部与左侧房间隔,作为快通路传导纤维使快径逆传具有多种出口。
4.连接蛋白43在房室结深层细胞表达阴性,而浅层细胞及中层细胞呈弱阳性可以帮助解释双重输入和或纵行分离,窦房结的冲动经心房组织传到房室结前上方的浅层细胞到达房室束,而适时的期前收缩由于不应期的影响在快径受阻,冲动沿界嵴在冠状窦口下缘传导至后延伸,后延伸具有结样细胞特性且连接蛋白43表达阴性,具有慢径传导的组织学及分子学基础,而后经致密结深层到达房室束,在结的后方可有电传导的出口,快慢径间由于传导速度不同导致纵向分离,为折返环的形成奠定了基础。双径路组冠状静脉窦与周围心房组织连接蛋白表达的差异造成传导速度不同,有可能为左、右心房电传导过程中形成折返奠定了结构基础。冠状窦Cx43表达的差异造成快径路逆向传导障碍可能是室上速诱发的限制因素。
综上所述,房室结存在多丛折返的组织学基础,而临床可表现为多种复杂的电生理现象,这为临床中常规消融未能成功的患者,在二尖瓣环的后侧及冠状窦内成功消融提供了理论依据。
Objective: To study the possible mechanism of atrioventricular nodal reentrant tachycardia by observing and detecting the morphology characteristic and Cx43 expression in coronary sinus and posterior extension .
Method: 20 New Zealand rabbits were divided into two groups by electro-physiological examination: dual-pathway group and non-dual-pathway group. In the former group, jump phenomenon or atrium / ventricle double reaction or atrioventricular nodal reentrant tachycardia was found out during electro-physiological stimulus, nor the later group. Then the preparation Includes coronary sinus and Koch's triangle was cut out and devided into two parts since 1mm from the coronary sinus ostium(CSO). Coronal sections apply to Koch's triangle in order to observe the morphology of PNE . The rest preparation was sliced by Sagittal plane. To observe Cx43 by H-E and immunohistochemistry of posterior extension and coronary sinus.Ipp6.0 was used to analysis quantitatively Cx43 expression ,then statistical analysis data by SPSS11.0 software .
Results:
1 .Electro-physiological stimulus:
Atrioventricular nodal reentrant tachycardial was induced in 5 rabbits during electro-physiological stimulus. There are 1 rabbit with jump phenomenon and 1 rabbit with ventricle double reaction were found out in 2 rabbits; There is no correlation between the size of Koch's triangle and the AV interval and the cycle of tachcardia in dual-pathway group.
2.Morphology:
(1) Coronary sinus was surrounded by myocardial coat, which become thin from CSO toward distal, even was covered only by epicardical fat or fibers. Compact node was consisted of two layers cell bundle. PNE was found by serial sections from compact node that is deep layer cells of AVN to CSO in all specimens. Three specimens have left posterior extension. Right posterior extension can be seen in all specimens. Cells in PNE were sparser compared with compact node.
3. Immunohistochemistry:
Cx43 express negative in deep atrioventricular node cells, weakly positive in superficial and intermediate cells. Cx43 express negative in posterior extention in both groups. coronary sinus myocardial coat Cx43 Positive expression in membrane. In dual-pathway group, coronary sinus expression of Cx43 are higher than left atrium. Non-dual-pathway group had no significant difference
Conclusion:
1. conduction of slow pathway has special structure rather than base on size of Koch's triangle.
2. Coronary sinus connect left atrium and right atrium by myocardial coat,which involve in reentrant cycle.
3. Compact node and posterior extension have characteristic of slow pathway. Dual A-V nodal pathways display when conduction of velocity or refractory changed. Due to there are more than one fast pathway, impulse propagation not only from deep layer of transitional cells to left atrial septum ,then reach to right atrium via of coronary sinus,but also from superficial layer of transitional cells to the top of Koch's triangle.
4. Cx43 negative express in deep atrioventricular node cells, weakly positive express in superficial and intermediate cells can explain longitudinal dissociation. Sinus impulse propagation from atrium to Superficial layer and middle layer cell bud dle ,then reach to His bundle. Premature systole block in the fastway because of refractory .The activation conduct from inferior margin of CSO to PNE, which have charateristics of nodal cells and express Cx43 negatively. After successful ablation of right posterior extension, the charateristics of slow conduction display in left posterior extension. Difference in morphology of coronary sinus and difference in expression of Cx43 maybe the pathology mechanism of AVNRT. We consider the block of reverse transmission is limiting factor of atrioventricular nodal reentranttachycardia.
Multiple phenomenon of electrophysiology seems easy to understand according to this view. The study on the possible mechanism of AVNRT can provide theoretical evidence for radiofrequency catheter ablation on different focal.
引文
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2.Racker DK.Atrioventricular node and input pathways:a correlated gross anatomical and histological study of the canine atrioventricular junctional region.Anat Rec.1989 Jul;224(3):336-54.
3.Inoue S,Becker AE.Posterior extensions of the human compact atrioventricular node:A neglected anstomic feature of potential clinical significance[J].Circulation,1998,97(2):188-193.
4.Anselme F,Papageorgion P,Monahan k,et al.Presence and significance of the left atrioventricular nodal reentrant tachycardia.Am J Cardial,1999,83(11):1530.
5.王祖禄,陈新.Jackman教授访华讲座纪要.中华心律失常杂志,2002,6(2):123-124.
6.Altemose GT,Scott LR,Miller JM.Atrioventricular nodal reentrant tachycardia requiring ablation on the mitral annulus.J Cardiovasc Electrophysiol,2000;11:1281-4.
7.Ayhan KILIC,Basri AMASYALI,Ersoy ISIK,et al.Atrioventricular Nodal Reentrant Tachycardia Ablated From Left Atrial Septum.Int Heart J,2005;46:1023-1031.2.Ong MG,Lee PC,Tai CT,et al.Coronary sinus morphology in different types of supraventricular tachycardias.J Interv Card Electrophysiol,2006 Jan;15(1):21-6.
8.OtomK,Nagata Y,Uno K,et al.Atypical atrioventricular nodal reentrant tachycardia with eccentric coronary sinus activation:electrophysiological characteristics and essential effects of left-sided ablation inside the coronary sinus.Heart Rhythm.2007 Apr;4(4):421-42.
9.Inoue S,Becker AE.Koch' s triangle sized up:anatomical landmarks in perspective of catheter ablation procedures.Pacing Clin Electrophysiol,1998,21(8):1553-1558.
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