探讨兔持续性房颤模型的建立方法及贝那普利对房颤的干预作用
|
摘要
背景
心房颤动(atrial fibrillation,AF,简称房颤)是临床上最常见的心律失常之一,也是21世纪心律失常学面临的主要难题。并发症如心房变性、心动过速性心肌病、心力衰竭、外周血管栓塞等可以给患者带来高致残率和高致死率。目前关于房颤的发病机制还不十分清楚,传统的治疗效果也不令人满意。大量研究表明肾素-血管紧张素-醛固酮系统(RAAS)参与房颤的形成和维持机制,可能为房颤的治疗指明新方向。RAAS效应激素血管紧张素Ⅱ (AngⅡ)和醛固酮(Ald)促进心肌和血管中层成纤维细胞分裂增殖,有促进Ⅰ型和Ⅲ型胶原纤维合成的作用。因此,抑制RAAS的药物可能会预防和减少房颤的发生,对寻找房颤抗重构治疗有重要的临床意义,且已成为目前研究的重点。
目的
探讨兔持续性心房颤动模型的建立方法及贝那普利对房颤的干预作用。
方法
30只新西兰兔,体重相仿,雌雄不限,随机分为3组,对照组：置入起搏器,但不起搏(n=10)；房颤模型组(简称房颤组)：置入起搏器+高频起搏左心耳(n=10)；贝那普利组：置入起搏器+高频起搏左心耳+贝那普利灌胃(n=10)。3组均行开胸术,左心耳心外膜下缝起搏电极,起搏器包埋于腹部皮下。对照组不起搏,房颤组与贝那普利组均持续快速起搏左心耳形成房颤模型,其中贝那普利组在手术当天开始以贝那普利5mg/g·d)灌胃,4周后观察各组心电图,其中对照组未出现房颤,房颤组10只均出现持续性房颤(房颤持续时间大于24小时),贝那普利组10中只有1只出现持续性房颤,4周后处死各组动物,电镜下观察各组心房肌细胞的超微结构改变,HE染色光镜下观察组织的改变并计算各组肌溶解比率,免疫组化Ⅲ型胶原并进行胶原半定量分析。
结果
1.心外膜下高频起搏左心耳建立兔持续性房颤模型成功率高,可操作性较强;
2.贝那普利组心房肌细胞溶解率低于房颤组(P<0.05),与对照组比较差异无统计学意义(P>0.05)：贝那普利组心房组织中Ⅲ型胶原含量明显低于房颤组,与对照组比较差异无统计学意义。
结论
1.心外膜下高频起搏左心耳可诱发兔持续性房颤模型方法可靠。
2.贝那普利可抗房颤心房的结构重构。
Background
Atrial fibrillation (AF) is one of the most common cardiac arrythmia, is also a main problem in the field in the21st century. Most patients with AF have many comorbidities such as atrial degeneration, tachycardia-induced cardiomyopathy, heart failure, peripheral embolism. The rate of mortality and disability of AF are higher. The pathogenesis of atrial fibrillation remains unclear at present, and the therapeutic effect of traditional treatment is not satisfactory. A large number of studies have shown that the renin-angiotensin-aldosterone system (RAAS) is involved in the formation and maintenance mechanisms of AF, and will indicate a new direction for the treatment of atrial fibrillation. RAAS effector hormone Ang II and Aid promote proliferation and division of ventricular and vascular fibroblast and the synthesis of type Ⅰ, Ⅲ collagen. Therefore, inhibition of RAAS drugs can prevent and reduce the occurrence of AF and has important clinical significance for looking for AF therapy. It is important to study the underlying mechanisms of AF and to identify therapeutic targets.
Objection
To establish the animal model of persistent atrial fibrillation (AF) and to study the benazepril intervention effects.
Methods
Thirty New Zealand rabbits (similar weight, male or female), were randomly divided into three groups, the control group (n=10)(pacemaker implantation, but not pacing), the atrial fibrillation model group (n=10)(pacemaker implantation and high frequency pacing the left atrial appendage), benazepril intervention group (n=10)(pacemaker implantation and high frequency pacing the left atrial appendage). All rabbits underwent thoracic surgery, the left atrial appendage epicardial pacing electrode was sutured, the pacemaker embedded in abdominal subcutaneous. The control group did not pace, the atrial fibrillation and benazepril group showed sustained rapid pacing, left atrial appendage formed the atrial fibrillation model. Rabbits in benazepril group was intragastrically administered5mg/(kg·d) benazepril beginning on the day of surgery, the electrocardiogram was observed after4weeks, the control group does not show atrial fibrillation, however, in atrial fibrillation group,10rabbits were persistent atrial fibrillation (AF duration greater than24hours); in benazepril group, only1showed persistent atrial fibrillation. All rabbits in each group were sacrificed after4weeks, atrial muscle tissues were fixed and sectioned for HE staining, and calculated the dissolved ratio, type III collagen was assayed by immunohistochemistry and semi-quantitative analysis. Atrial muscle cell ultrastructural changes were observed under electron microscope.
Results
Rabbit persistent atrial fibrillation modeling had a high success rate under high-frequency epicardial pacing the left atrial appendage and it is easy to operate. Dissolution rate of atrial muscle cells in benazepril group was lower than that in atrial fibrillation group (P<0.05), however, there was no significant difference compared to control group (P>0.05). The levels of type III collagen of atrial tissues in benazepril group was significantly lower than those in atrial fibrillation group, while there was no significant difference compared to control group.
Conclusions
The method of establishing rabbit persistent atrial fibrillation model under high-frequency epicardial pacing the left atrial appendage is reliable. Benazepril can block structural remodeling of AF.
心房颤动(atrial fibrillation,AF,简称房颤)是临床上最常见的心律失常之一,也是21世纪心律失常学面临的主要难题。并发症如心房变性、心动过速性心肌病、心力衰竭、外周血管栓塞等可以给患者带来高致残率和高致死率。目前关于房颤的发病机制还不十分清楚,传统的治疗效果也不令人满意。大量研究表明肾素-血管紧张素-醛固酮系统(RAAS)参与房颤的形成和维持机制,可能为房颤的治疗指明新方向。RAAS效应激素血管紧张素Ⅱ (AngⅡ)和醛固酮(Ald)促进心肌和血管中层成纤维细胞分裂增殖,有促进Ⅰ型和Ⅲ型胶原纤维合成的作用。因此,抑制RAAS的药物可能会预防和减少房颤的发生,对寻找房颤抗重构治疗有重要的临床意义,且已成为目前研究的重点。
目的
探讨兔持续性心房颤动模型的建立方法及贝那普利对房颤的干预作用。
方法
30只新西兰兔,体重相仿,雌雄不限,随机分为3组,对照组：置入起搏器,但不起搏(n=10)；房颤模型组(简称房颤组)：置入起搏器+高频起搏左心耳(n=10)；贝那普利组：置入起搏器+高频起搏左心耳+贝那普利灌胃(n=10)。3组均行开胸术,左心耳心外膜下缝起搏电极,起搏器包埋于腹部皮下。对照组不起搏,房颤组与贝那普利组均持续快速起搏左心耳形成房颤模型,其中贝那普利组在手术当天开始以贝那普利5mg/g·d)灌胃,4周后观察各组心电图,其中对照组未出现房颤,房颤组10只均出现持续性房颤(房颤持续时间大于24小时),贝那普利组10中只有1只出现持续性房颤,4周后处死各组动物,电镜下观察各组心房肌细胞的超微结构改变,HE染色光镜下观察组织的改变并计算各组肌溶解比率,免疫组化Ⅲ型胶原并进行胶原半定量分析。
结果
1.心外膜下高频起搏左心耳建立兔持续性房颤模型成功率高,可操作性较强;
2.贝那普利组心房肌细胞溶解率低于房颤组(P<0.05),与对照组比较差异无统计学意义(P>0.05)：贝那普利组心房组织中Ⅲ型胶原含量明显低于房颤组,与对照组比较差异无统计学意义。
结论
1.心外膜下高频起搏左心耳可诱发兔持续性房颤模型方法可靠。
2.贝那普利可抗房颤心房的结构重构。
Background
Atrial fibrillation (AF) is one of the most common cardiac arrythmia, is also a main problem in the field in the21st century. Most patients with AF have many comorbidities such as atrial degeneration, tachycardia-induced cardiomyopathy, heart failure, peripheral embolism. The rate of mortality and disability of AF are higher. The pathogenesis of atrial fibrillation remains unclear at present, and the therapeutic effect of traditional treatment is not satisfactory. A large number of studies have shown that the renin-angiotensin-aldosterone system (RAAS) is involved in the formation and maintenance mechanisms of AF, and will indicate a new direction for the treatment of atrial fibrillation. RAAS effector hormone Ang II and Aid promote proliferation and division of ventricular and vascular fibroblast and the synthesis of type Ⅰ, Ⅲ collagen. Therefore, inhibition of RAAS drugs can prevent and reduce the occurrence of AF and has important clinical significance for looking for AF therapy. It is important to study the underlying mechanisms of AF and to identify therapeutic targets.
Objection
To establish the animal model of persistent atrial fibrillation (AF) and to study the benazepril intervention effects.
Methods
Thirty New Zealand rabbits (similar weight, male or female), were randomly divided into three groups, the control group (n=10)(pacemaker implantation, but not pacing), the atrial fibrillation model group (n=10)(pacemaker implantation and high frequency pacing the left atrial appendage), benazepril intervention group (n=10)(pacemaker implantation and high frequency pacing the left atrial appendage). All rabbits underwent thoracic surgery, the left atrial appendage epicardial pacing electrode was sutured, the pacemaker embedded in abdominal subcutaneous. The control group did not pace, the atrial fibrillation and benazepril group showed sustained rapid pacing, left atrial appendage formed the atrial fibrillation model. Rabbits in benazepril group was intragastrically administered5mg/(kg·d) benazepril beginning on the day of surgery, the electrocardiogram was observed after4weeks, the control group does not show atrial fibrillation, however, in atrial fibrillation group,10rabbits were persistent atrial fibrillation (AF duration greater than24hours); in benazepril group, only1showed persistent atrial fibrillation. All rabbits in each group were sacrificed after4weeks, atrial muscle tissues were fixed and sectioned for HE staining, and calculated the dissolved ratio, type III collagen was assayed by immunohistochemistry and semi-quantitative analysis. Atrial muscle cell ultrastructural changes were observed under electron microscope.
Results
Rabbit persistent atrial fibrillation modeling had a high success rate under high-frequency epicardial pacing the left atrial appendage and it is easy to operate. Dissolution rate of atrial muscle cells in benazepril group was lower than that in atrial fibrillation group (P<0.05), however, there was no significant difference compared to control group (P>0.05). The levels of type III collagen of atrial tissues in benazepril group was significantly lower than those in atrial fibrillation group, while there was no significant difference compared to control group.
Conclusions
The method of establishing rabbit persistent atrial fibrillation model under high-frequency epicardial pacing the left atrial appendage is reliable. Benazepril can block structural remodeling of AF.
引文
[1]Prystowsky EN. Perspectives and controversies in atrial fibrillation.Am J Cariol,1998,82 (4A):3I-6I.
[2]黄从新.经导管消融治疗心房颤动的现状与展望.中华心律失常杂志,2005,9(2)：87-92.
[3]Kalman JM, Power JM, Chen JM, et al. Importance of electrode design, lead configuration and impedance for successful low energy transcatheter atrial defibrillation in dogs. J Am Coil Cardiol,1993,22:1199-1206.
[4]梁兆光,姜玉萍,刘和平.低通气量房颤模型的建立.中国心脏起搏与心电生理杂志,1998,12：132-133.
[5]Kannel WP, Abbott RD Savage DD.et al. Epidemiologic features of atrial fibrillation:the Framingham study. N Engl J Med,1982,306:1018-1022.
[6]Smith PK, HoIman WL, Cox JL. Surgical treatment of superventrieular tachyarrhythmias. Surg Clin North Am,1985,65:553-570.
[7]Allessie M, Kirchhof C, Scheffer GJ, et al. Regional contrl of atrial fibrillation by rapid Pacing in conscious dog. J Circulation,1991,84(4) 1689-1697.
[8]Wijiffel MC, Kirchh CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation.1995,92(7):1954-1968.
[9]Morillo CA, Klein GJ, Jones DL, et al. Chronic rapid atrial pacing:a structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. Circulation,1995,91:1588-1595.
[10]Lijnen P, Petrov V Antagonism of the renin-angiotensin-aldosterone system and collagen metabolism in cardiac fibroblasts. Methods Find Exp Clin Pharmacol.1999, 21(3):215-227.
[11]Ramires FJ, Sun Y, Weber KT. Myocardial fibrosis associated with aldosterone or angiotensin Ⅱ administration:attenuation by calcium channel blockade. J Mol Cell Cardiol,1998,30(3):475-483.
[12]Gampbell SE, Katwa LC. Angiotensin Ⅱ stimulated expression of transforming growth factor beta-1 in cardiac fibroblasts and myofibroblasts. J Med Cell Cardiol,1997,29(7): 1947-1958.
[13]Moe GK, Abildskov JA. Artial fibrillation as a self-sustaining arrhythmia independent of focal discharge. J Am Heart,1959,58:59-70.
[14]Liu J, Huang CX, Bao MW, et al. Ectopic activity induced by atrial pressure in rabbit pulmonary vein in vitro. Chin Med J,2005,118:1210-1213.
[15]Jais P, Haissaguerre M, Shah DC, et al. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation,1997,95:527-576.
[16]Haissaguerre M, Shah DC, et al. Electrophysiological breakthroughs from the atrium to the pulmonary veins. Circulation,2000,102:2463-2465.
[17]王烯,黄从新,江洪,等.兔肺静脉心肌袖组织学特性研究.中华心律失常学杂志,2003,7：241-243.
[18]Chen Y J, Chen SA, Tai CT, et al. Role of atrial electrophyisology and autonomic nervous system in patients with superventricuiar tachy cardia and paroxysmal atrial fibrillation. J Am Coll Cardiol,1998,32:732-737.
[19]Coumel P. Neurogenic and humoral influences of the autonomic nerous system in the determination of paroxysmal atrial fibrillation. In:Atteul P, Coumel P, Janse MJ, editors. The atrium in health and disease. Mount Kiso, NY:Futura Publishing Co,1989:213-232.
[20]Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation,1997,96:1180-1184.
[21]Ausma J, van der Velden HM, Lenders MH, et al. Reverse structural and gap-junctional remodeling after prolonged atrial fibrillation in the goat. Circulation,2003,107: 2051-2058.
[22]Bosch RF, Grammer JB, Kuhlkamp V, et al. Electrical remodeling in atrial fibrillation-cellular and molecular mechanisms. Z Kardiol,2000,89:795-802.
[23]White CW, Kerver RE, Weiss HR, et al. The effect of atrial fibrillation on atrial pressure-volume and flowrelationship. OreRes,1982,51:205-215.
[24]Van Wagoner DR, Pond AL, Lamorgese M, et al. Atrial L-type ca2+currents and human atrial fibrillation. Circ Res,1999,85:428-436.
[25]Ausma J, Dispersyn GD, Duimel H, et al. Changes in ultrastructrual calcium distribution in goat atria during atrial fibrillation. J Mol Cell Cardiol,2000,32:355-364.
[26]Van Wagoner DR, Nerbonne JM. Molecular basis of electrial remodeling in artial fibrillation. J Mol cell Cardiol,2000,32:1101-1117.
[27]Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation,1997,96:1180-1184.
[28]Li D, Farch S, Leung TK, et al. Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort. Circulation,1999(7),100:87-95.
[29]Yu WC, Lee SH, Tai CH, et al. Reversal of atrial electrial remodeling following cadioversion of long-standing atrial fibrillation in man. Cardiovasc Res,1999, 42:470-476.
[30]Verheule S, Sato T, et al. Increased vulnerability to atrail fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-betal. Circ Res, 2004,94:1458-1465.
[31]单兆亮,王玉堂,时向民,等.持续性心房颤动山羊模型的心房单极电极标测.中国心脏起搏与心电生理杂志.2002,16(3)：212-215.
[32]Pelouch V, Dixon IMC, Golfman L, et al. Role of extracellular matrix proteins in heart function. MoI Cell Biochern,1994.129:101-120.
[33]Borg TK, Burgess ML, Holding it all together:organization and function of the extracellular matrix in the heart. Heart failure,1993,9:230-238.
[34]Van der Rest M,Garrone R Collagen family of proteins. FASEB J,1991,5:2814-2823.
[35]Bashey RI,Martinez-Hemandez A, Jimenez SA. Isolation,characterization, and localiza-tion of cardiac collagen type VI. Associations with other extracellular matrix componen-ts. Circ Res,1992,70:1006-1017.
[36]Weber KT, Brilla CG, Janicki JS, Myocardial fibrisis:functional significance and regulato-ry factor. Cardiovasc Res,1993,27:341-348.
[37]Weber KT. Cardiac interstitium in health and disease. J Am Coil Cardiol,1989,13: 1637-1652.
[38]Borg TK, Burgess ML, Holding it all together:organization and function of the extracellu-lar matrix in the heart. Heart failure,1993,9:230-238.
[39]Boixel C, Fontaine V, Rucker-Marin C, et al. Fibrosis of the left atria during progres-sion of heart failure is associated with increased matrix metalloproteinases in the rat. J Am Coll Cardiol,2003,42:336-344.
[40]Kuwahara F, Kai H, Tokuda K, et al. Transforming growth factor-beta function blocking prevents myocardial fibrosis and diastolic dysfunction in pressure overloaded rats. Circu-ltion,2002,106:130-135.
[41]Tamirisa P, Frishman WH, Kumar A. Endothelin and andothclin antagonism:roles in card-iovascular health and disease. Am Heart J,1995,130:601-610.
[42]Li PF, Dietz R, von Harsdorf R, et al. Superoxide induces apoptosis in cardiomyo-cytes, but proliferation and expression of transforming growth factor beta in cardiac fibroblast. FEBS-Lett,1999,488:206-210.
[43]Weber KT. Cardiac interstitium in health and disease:the fibrillar collagen network. J Am Coll,1989,13:1637-1652.
[44]Hordof AJ, Edie R, Malm JR,et al. Electrophysiologic properties and response to pharma-cologic agents of fibers from diseased human atria.Circulation,1976,54:774-779.
[45]Attuel P, Chiders R, Cauchemez B, et al. Failure in the rate adaptation of the atrial refractory period:its relationship to vulnerability. Int J Cardiol,1982,179-197.
[46]Allessie M, Koning K, Wijiffels M. Electrophysiological mechanism of atrial Fibrillation. In:Dimarco JP, Prystowsky EN, editors. Atrial Arrhythmias:State of Art. Armonk, NY: Futura,1995:155-161.
[47]Schoaen U, Ausma J, Stellbrink C, et al. Cellular mechamisms of depressed atrial contractility in patients with chronic atrial fibrillation. Circulation,2001,103:691-698.
[48]Sun H, Chartier D, Leblanc N, et al. Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes. Cardiovasc Res,2001, 49:751-761.
[49]Allessie MA. Atrial electrophysiologic remodeling:another vircle. J Cardiovasc Electrophysiol,1998,9:1378-1393.
[50]Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol, 2003,41:2197-204.
[51].Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res,2002,54:230-246.
[52]Nattel S. New ideas about atrial fibrillation 50 years on. Nature,2002,415:219-226.
[53]Madrid AH, Bueno MG, Rebollo JMG, et al. Use of irhesartan to maintain sinus rhyhm in patients with long-lasting Persistent atrial fibrillation. Circulation,2002,106:331-336.
[54]Vermes E, Tardif JC, Bourassa MG, et al. Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction. Circulation,2003,107:2926-2931.
[55]Ueng KC, Tsai TP, Yu WC, et al. Use of enalapril to facilitate sinus rhythm maintenan-ce after external cardiovcrsion of long-standing persistent atrial fibrillation. Results of a prospective and controlled study. Eur Heart J,2003,24:2090-2098.
[56]Goette A, Staack T, Rocken C, et al. Increased expression of extracellular signal regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation[J]. J Am Coll,2000,35:1669-1677.
[57]Burstein B, Nattel S,Atrial fibrosis:mechanisms and clinical relevance in atrial fibrillation[J]. J Am Coll,2008,51:80-809.
[58]Iwata M, Cowling RT, Gurantz D, et al. Angiotensin-(1-7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects[J]. Am J Physiol Heart Circ Physiol,2005,289:H2356-H2363.
[59]Grobe JL, Mecca Ap,Lingis M, et al.prevention of angiontensin Ⅱ-induced cardiac remodeling by angiotensin-(1-7). Am J Physiol CircPhysiol,2007,292:H736-H742.
[60]Connell JM, Davies E. The nw biology of adosterone. Endocrinol,2005,186:1.
[61]Shimizu M, Tanaka R, Uchida M, et al. Effect of angiotensin Ⅱ type 1 receptor blocker on cardiac angiotensin eonverting enzyme and chymase-like activities, and cardiac fibrosis in cardiomyopathic hamsters[J]. J Vet Med Sci,2006,68:227-233.
[62]LI D, Shinagawa K, Pang L, et al. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation,2001,104:2608-2614.
[63]Horiuchi M, Akishita M, Dxau VJ. Recent progress in angiotensin II type 2 receptor research in the cardiovascular system. Hypertension,1999,33:613-621.
[64]Senbonmatsu T, Ichihara S, Price E Jr, et al. Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload. J Clin Invest, 2000,106(3):R25-R29.
[65]Yamada H, Horiuchi M, Akishita M, et al. Regulation of vascular develoment and differentiation by angiotensin II type 2 receptor. Hypertension,1997,30:470-475.
[66]Yamada T, Akishita M, Pollman M, et al. Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis and antagomize angiotensin type 1 receptor action:an in vitro gene transfer study. Life Sci,1998,63:PL289-PL295.
[67]Dimmeler S, Rippmann V, Weiland U, et al. Angiotensin II induces apoptosis of human endothelial cells:protective effect of nitric oxide. Circ Res,1997,81:970-976.
[1]Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention:the Anticoagulation and Risk Factors in Atrial Fibrillation(ATRIA) Study. JAMA,2001,285(18): 2370-2375.
[2]周自强,胡大一,陈捷,等.中国心房颤动现状的流行病学研究[J].中华内科志,2004,43(7)：491-494.
[3]Wolf PA, AbboR RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke:The Framingham Study[J]. Stroke,1991,22(8):983-988.
[4]Coumel P. Neural aspects of paroxysmal atrial fibrilfation. In:Falk RH, Podrid PJ, eds. Atrial fibrillation:Mechanisms and anagement. NewYork:Raven Press.1992:109-125.
[5]Bellet S. Clinical disorders of the heart beat.3rd ed. Philadelphia:1971:1-90.
[6]Prystowsky EN, Katz AM. Atrial fibrillation. In:Topoi Eseds. Text, book of cardio-vascular Madcine. Philadelphia:Lippincott—Raven,1998:1661.
[7]Levy S, Breithardt G, Campbell RW, et al, Atrial fibrillation:current knowledge and recommendations for management. Working Group on Arrhythmias of the European Society of Cardiology. Ear Heart J,1998,19:1294-1320.
[8]AllessieMA, Konings KT, Kirchhof CJ, Mapping of atrial fibrillation. In:Olsson SB, Allessie MA, Campbell RW. Atrial fibrillation mechanisms and therapeutic strategies. New York:Futurg.1994:37-49.
[9]Levy S, Novella P, Ricard P, et al. Paroxysmal atrial fibrillation:a need for classifica-tion. J Cardiovasc Electrophysiol,1995,6:69-74.
[10]Sopher SM, Camm AJ. Therapy for atrial fibrillation:control of the ventricular resp-onse and prevention of recurrence. Coron Artery Dis,1995,6:106-114.
[11]LevyS. Classification system of atrial fibrillation. Curr odin Cardiol,2000,15:54-57.
[12]Watfigney WA, Meusab GA, Croft JB. Increasing trends in hospitalization for atrial fibrillation in the United States,1985 through 1999 implications for primary prev-ention. Circulation,2003,108:711-716.
[13]Wolf PA, Mitchell JB, Baker CS. et al. Impact of atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med,1998,158:229-234.
[14]Ringborg A, Nieuwlant R, Lindgren P, et al. Costs of atrial fibrillation in five European countries:results from the Euro Heart Survey on atrial fibrillation. Europace,2008,10: 403-411.
[15]Qi WH. Retrospective investigation of hospitalized patients with atrial fibrillation in ma-inland China. Int J Cardiol,2005,105:283-287.
[16]刘英明,朱智明,曹毅,等.阻断肾素-血管紧张素系统对高血压患者心房颤动发生 危险的影响.中国脏起搏与心电生理杂志,2005,19(4)：264.
[17]LI D, Shinagawa K, Pang L, et al. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing induced congestive heart failure. Circulation,2001,104:2608-2614.
[18]Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angio-tensin converting enzyme inhibitors and angiotensin receptor blockers. Journal of the American College of Cardiology,2005,45(11):1832.
[19]Pedersen OD, Bagger H, Kober L, et al. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients wim left ventricular dysfunc-tion. Circulation,1999,100:376-380.
[20]Palardy M, Ducharme A, Nattel S, et al. Absence of protective effect of reninangiotensin system inhibitors on atrial fibrillation development:insights from the Canadian trial of atrial fibrillation (CTAF). Can J Cardiol,2008,24:709-713.
[21]Nakashima H, Kumagai K, Urata H, et al. Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation,2000,101:2612-2617.
[22]Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol, 2003,41:2197-2204.
[23]Akashiba A, Ono H, Ono Y, et al. Valsartan improve LNAME exacerbatedcardiac fibro-sis with TGF-beta inhibition and apoptosis induction inspontaneously hypertensive rats.J cardiol,2008,52:239-246.
[24]刘恩照,李广平,徐昭,李健,杨胜荣,杨万松《中国心脏起搏与心电生理杂志》ISTICPKU-2010年2期
[25]万里燕,崔建,李亮,魏建英,李松鹤.血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗药预防高血压患者房颤发生的Meta分析.《中国药房》2010年第10期.
[26]Disertori M, Latini R, Barlera S, et al. Valsartan for prevention of recurrent atrial fibrilla-tion.N Engl J Med,2009,360:1606-1617
[27]王涛林培林李雅男实用心脑肺血管病杂志2007年9月第15卷第9期
[28]殷跃辉,刘增长,吴近近,等.胺碘酮与氯沙坦、培哚普利联合治疗阵发性心房颤动的前瞻、随机开放研究.中华心血管病杂志,2006,34：299-302.
[29]雷涛,刘小慧,罗太阳,李晖,谷孝艳,陈东,王伟,王海云《心肺血管病杂志》2010年5月.
[30]RobertV,Besse S,Sabri A,et al.Differential regulation of matrix metailoproteinases associated with aging and hypertension in the rat heart, hb Invest,1997, 76:729-738.
[31]Milliez P. Girerd X. Plottin PF, et al. Evidenee for an increase rate of cardiovascular events in patients, ts with primary aldosteromim. J Am Coil Cardiol.2005.45: 1243-1248.
[32]Yang SS, Han W, Zhou HY, et al. Effects of spironolactone on electrical and structural remodeling of atrium in congestive heart failure dogs. Chin Med J (Engl),2008,121: 38-42.
[33]顾磊,王联发,罗骏,周文兵.《中华全科医学》2011年8月第9卷第8期
[34]Shimizu M, Tanaka R, Uchida M, et al. Effect of angiotensin II type 1 receptor blocker on cardiac angiotensin eonverting enzyme and chymase-like activities, and cardiac fibrosis in cardiomyopathic hamsters[J]. J Vet Med Sci,2006,68:227-233.
[35]Lai LP,Su MJ,Lin JL,et al.Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban. J Am Coil of Cardio,1999,33(5):1231.
[36]Yue Li,Feng J,Gaspo R,et al.Ionic remodeling underlying action potential changes in a canine model of Atrial fibrillation. Circ Res,1997,81(4):512-525.
[37]Tieleman RG,De Langen C,Van Gelder IC,et al.Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation,1997,95(7):1945-1950.
[38]Yu WC.Chen SA,Lee SH.Tachycardia-Induced Change of Atrial Refractory Period in Humans:Rate Dependency and Effects of Antiarrhythmic Drugs. Circulation 1998,97 (23):2331-2337.
[39]de Simone A,Stabile QVitale DF,et al.Pretreatment with verapamil inpatients with persis-tent or chronic atrial fibrillation who underwent electrical cardioversion. J Am Coll Cardiol,1999,34(5):810-814.
[40]Fareh S,Benardeau A,Thibault B.The T-Type Ca2+channel blocker mibefradil prevents the development of a substrate for atrial fibrillation by tachycardia-induced atrial remodeling in dogs. Circulation,1999,100(21):2191-2197.
[2]黄从新.经导管消融治疗心房颤动的现状与展望.中华心律失常杂志,2005,9(2)：87-92.
[3]Kalman JM, Power JM, Chen JM, et al. Importance of electrode design, lead configuration and impedance for successful low energy transcatheter atrial defibrillation in dogs. J Am Coil Cardiol,1993,22:1199-1206.
[4]梁兆光,姜玉萍,刘和平.低通气量房颤模型的建立.中国心脏起搏与心电生理杂志,1998,12：132-133.
[5]Kannel WP, Abbott RD Savage DD.et al. Epidemiologic features of atrial fibrillation:the Framingham study. N Engl J Med,1982,306:1018-1022.
[6]Smith PK, HoIman WL, Cox JL. Surgical treatment of superventrieular tachyarrhythmias. Surg Clin North Am,1985,65:553-570.
[7]Allessie M, Kirchhof C, Scheffer GJ, et al. Regional contrl of atrial fibrillation by rapid Pacing in conscious dog. J Circulation,1991,84(4) 1689-1697.
[8]Wijiffel MC, Kirchh CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation.1995,92(7):1954-1968.
[9]Morillo CA, Klein GJ, Jones DL, et al. Chronic rapid atrial pacing:a structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation. Circulation,1995,91:1588-1595.
[10]Lijnen P, Petrov V Antagonism of the renin-angiotensin-aldosterone system and collagen metabolism in cardiac fibroblasts. Methods Find Exp Clin Pharmacol.1999, 21(3):215-227.
[11]Ramires FJ, Sun Y, Weber KT. Myocardial fibrosis associated with aldosterone or angiotensin Ⅱ administration:attenuation by calcium channel blockade. J Mol Cell Cardiol,1998,30(3):475-483.
[12]Gampbell SE, Katwa LC. Angiotensin Ⅱ stimulated expression of transforming growth factor beta-1 in cardiac fibroblasts and myofibroblasts. J Med Cell Cardiol,1997,29(7): 1947-1958.
[13]Moe GK, Abildskov JA. Artial fibrillation as a self-sustaining arrhythmia independent of focal discharge. J Am Heart,1959,58:59-70.
[14]Liu J, Huang CX, Bao MW, et al. Ectopic activity induced by atrial pressure in rabbit pulmonary vein in vitro. Chin Med J,2005,118:1210-1213.
[15]Jais P, Haissaguerre M, Shah DC, et al. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation,1997,95:527-576.
[16]Haissaguerre M, Shah DC, et al. Electrophysiological breakthroughs from the atrium to the pulmonary veins. Circulation,2000,102:2463-2465.
[17]王烯,黄从新,江洪,等.兔肺静脉心肌袖组织学特性研究.中华心律失常学杂志,2003,7：241-243.
[18]Chen Y J, Chen SA, Tai CT, et al. Role of atrial electrophyisology and autonomic nervous system in patients with superventricuiar tachy cardia and paroxysmal atrial fibrillation. J Am Coll Cardiol,1998,32:732-737.
[19]Coumel P. Neurogenic and humoral influences of the autonomic nerous system in the determination of paroxysmal atrial fibrillation. In:Atteul P, Coumel P, Janse MJ, editors. The atrium in health and disease. Mount Kiso, NY:Futura Publishing Co,1989:213-232.
[20]Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation,1997,96:1180-1184.
[21]Ausma J, van der Velden HM, Lenders MH, et al. Reverse structural and gap-junctional remodeling after prolonged atrial fibrillation in the goat. Circulation,2003,107: 2051-2058.
[22]Bosch RF, Grammer JB, Kuhlkamp V, et al. Electrical remodeling in atrial fibrillation-cellular and molecular mechanisms. Z Kardiol,2000,89:795-802.
[23]White CW, Kerver RE, Weiss HR, et al. The effect of atrial fibrillation on atrial pressure-volume and flowrelationship. OreRes,1982,51:205-215.
[24]Van Wagoner DR, Pond AL, Lamorgese M, et al. Atrial L-type ca2+currents and human atrial fibrillation. Circ Res,1999,85:428-436.
[25]Ausma J, Dispersyn GD, Duimel H, et al. Changes in ultrastructrual calcium distribution in goat atria during atrial fibrillation. J Mol Cell Cardiol,2000,32:355-364.
[26]Van Wagoner DR, Nerbonne JM. Molecular basis of electrial remodeling in artial fibrillation. J Mol cell Cardiol,2000,32:1101-1117.
[27]Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation,1997,96:1180-1184.
[28]Li D, Farch S, Leung TK, et al. Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort. Circulation,1999(7),100:87-95.
[29]Yu WC, Lee SH, Tai CH, et al. Reversal of atrial electrial remodeling following cadioversion of long-standing atrial fibrillation in man. Cardiovasc Res,1999, 42:470-476.
[30]Verheule S, Sato T, et al. Increased vulnerability to atrail fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-betal. Circ Res, 2004,94:1458-1465.
[31]单兆亮,王玉堂,时向民,等.持续性心房颤动山羊模型的心房单极电极标测.中国心脏起搏与心电生理杂志.2002,16(3)：212-215.
[32]Pelouch V, Dixon IMC, Golfman L, et al. Role of extracellular matrix proteins in heart function. MoI Cell Biochern,1994.129:101-120.
[33]Borg TK, Burgess ML, Holding it all together:organization and function of the extracellular matrix in the heart. Heart failure,1993,9:230-238.
[34]Van der Rest M,Garrone R Collagen family of proteins. FASEB J,1991,5:2814-2823.
[35]Bashey RI,Martinez-Hemandez A, Jimenez SA. Isolation,characterization, and localiza-tion of cardiac collagen type VI. Associations with other extracellular matrix componen-ts. Circ Res,1992,70:1006-1017.
[36]Weber KT, Brilla CG, Janicki JS, Myocardial fibrisis:functional significance and regulato-ry factor. Cardiovasc Res,1993,27:341-348.
[37]Weber KT. Cardiac interstitium in health and disease. J Am Coil Cardiol,1989,13: 1637-1652.
[38]Borg TK, Burgess ML, Holding it all together:organization and function of the extracellu-lar matrix in the heart. Heart failure,1993,9:230-238.
[39]Boixel C, Fontaine V, Rucker-Marin C, et al. Fibrosis of the left atria during progres-sion of heart failure is associated with increased matrix metalloproteinases in the rat. J Am Coll Cardiol,2003,42:336-344.
[40]Kuwahara F, Kai H, Tokuda K, et al. Transforming growth factor-beta function blocking prevents myocardial fibrosis and diastolic dysfunction in pressure overloaded rats. Circu-ltion,2002,106:130-135.
[41]Tamirisa P, Frishman WH, Kumar A. Endothelin and andothclin antagonism:roles in card-iovascular health and disease. Am Heart J,1995,130:601-610.
[42]Li PF, Dietz R, von Harsdorf R, et al. Superoxide induces apoptosis in cardiomyo-cytes, but proliferation and expression of transforming growth factor beta in cardiac fibroblast. FEBS-Lett,1999,488:206-210.
[43]Weber KT. Cardiac interstitium in health and disease:the fibrillar collagen network. J Am Coll,1989,13:1637-1652.
[44]Hordof AJ, Edie R, Malm JR,et al. Electrophysiologic properties and response to pharma-cologic agents of fibers from diseased human atria.Circulation,1976,54:774-779.
[45]Attuel P, Chiders R, Cauchemez B, et al. Failure in the rate adaptation of the atrial refractory period:its relationship to vulnerability. Int J Cardiol,1982,179-197.
[46]Allessie M, Koning K, Wijiffels M. Electrophysiological mechanism of atrial Fibrillation. In:Dimarco JP, Prystowsky EN, editors. Atrial Arrhythmias:State of Art. Armonk, NY: Futura,1995:155-161.
[47]Schoaen U, Ausma J, Stellbrink C, et al. Cellular mechamisms of depressed atrial contractility in patients with chronic atrial fibrillation. Circulation,2001,103:691-698.
[48]Sun H, Chartier D, Leblanc N, et al. Intracellular calcium changes and tachycardia-induced contractile dysfunction in canine atrial myocytes. Cardiovasc Res,2001, 49:751-761.
[49]Allessie MA. Atrial electrophysiologic remodeling:another vircle. J Cardiovasc Electrophysiol,1998,9:1378-1393.
[50]Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol, 2003,41:2197-204.
[51].Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res,2002,54:230-246.
[52]Nattel S. New ideas about atrial fibrillation 50 years on. Nature,2002,415:219-226.
[53]Madrid AH, Bueno MG, Rebollo JMG, et al. Use of irhesartan to maintain sinus rhyhm in patients with long-lasting Persistent atrial fibrillation. Circulation,2002,106:331-336.
[54]Vermes E, Tardif JC, Bourassa MG, et al. Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction. Circulation,2003,107:2926-2931.
[55]Ueng KC, Tsai TP, Yu WC, et al. Use of enalapril to facilitate sinus rhythm maintenan-ce after external cardiovcrsion of long-standing persistent atrial fibrillation. Results of a prospective and controlled study. Eur Heart J,2003,24:2090-2098.
[56]Goette A, Staack T, Rocken C, et al. Increased expression of extracellular signal regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation[J]. J Am Coll,2000,35:1669-1677.
[57]Burstein B, Nattel S,Atrial fibrosis:mechanisms and clinical relevance in atrial fibrillation[J]. J Am Coll,2008,51:80-809.
[58]Iwata M, Cowling RT, Gurantz D, et al. Angiotensin-(1-7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects[J]. Am J Physiol Heart Circ Physiol,2005,289:H2356-H2363.
[59]Grobe JL, Mecca Ap,Lingis M, et al.prevention of angiontensin Ⅱ-induced cardiac remodeling by angiotensin-(1-7). Am J Physiol CircPhysiol,2007,292:H736-H742.
[60]Connell JM, Davies E. The nw biology of adosterone. Endocrinol,2005,186:1.
[61]Shimizu M, Tanaka R, Uchida M, et al. Effect of angiotensin Ⅱ type 1 receptor blocker on cardiac angiotensin eonverting enzyme and chymase-like activities, and cardiac fibrosis in cardiomyopathic hamsters[J]. J Vet Med Sci,2006,68:227-233.
[62]LI D, Shinagawa K, Pang L, et al. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation,2001,104:2608-2614.
[63]Horiuchi M, Akishita M, Dxau VJ. Recent progress in angiotensin II type 2 receptor research in the cardiovascular system. Hypertension,1999,33:613-621.
[64]Senbonmatsu T, Ichihara S, Price E Jr, et al. Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload. J Clin Invest, 2000,106(3):R25-R29.
[65]Yamada H, Horiuchi M, Akishita M, et al. Regulation of vascular develoment and differentiation by angiotensin II type 2 receptor. Hypertension,1997,30:470-475.
[66]Yamada T, Akishita M, Pollman M, et al. Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis and antagomize angiotensin type 1 receptor action:an in vitro gene transfer study. Life Sci,1998,63:PL289-PL295.
[67]Dimmeler S, Rippmann V, Weiland U, et al. Angiotensin II induces apoptosis of human endothelial cells:protective effect of nitric oxide. Circ Res,1997,81:970-976.
[1]Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention:the Anticoagulation and Risk Factors in Atrial Fibrillation(ATRIA) Study. JAMA,2001,285(18): 2370-2375.
[2]周自强,胡大一,陈捷,等.中国心房颤动现状的流行病学研究[J].中华内科志,2004,43(7)：491-494.
[3]Wolf PA, AbboR RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke:The Framingham Study[J]. Stroke,1991,22(8):983-988.
[4]Coumel P. Neural aspects of paroxysmal atrial fibrilfation. In:Falk RH, Podrid PJ, eds. Atrial fibrillation:Mechanisms and anagement. NewYork:Raven Press.1992:109-125.
[5]Bellet S. Clinical disorders of the heart beat.3rd ed. Philadelphia:1971:1-90.
[6]Prystowsky EN, Katz AM. Atrial fibrillation. In:Topoi Eseds. Text, book of cardio-vascular Madcine. Philadelphia:Lippincott—Raven,1998:1661.
[7]Levy S, Breithardt G, Campbell RW, et al, Atrial fibrillation:current knowledge and recommendations for management. Working Group on Arrhythmias of the European Society of Cardiology. Ear Heart J,1998,19:1294-1320.
[8]AllessieMA, Konings KT, Kirchhof CJ, Mapping of atrial fibrillation. In:Olsson SB, Allessie MA, Campbell RW. Atrial fibrillation mechanisms and therapeutic strategies. New York:Futurg.1994:37-49.
[9]Levy S, Novella P, Ricard P, et al. Paroxysmal atrial fibrillation:a need for classifica-tion. J Cardiovasc Electrophysiol,1995,6:69-74.
[10]Sopher SM, Camm AJ. Therapy for atrial fibrillation:control of the ventricular resp-onse and prevention of recurrence. Coron Artery Dis,1995,6:106-114.
[11]LevyS. Classification system of atrial fibrillation. Curr odin Cardiol,2000,15:54-57.
[12]Watfigney WA, Meusab GA, Croft JB. Increasing trends in hospitalization for atrial fibrillation in the United States,1985 through 1999 implications for primary prev-ention. Circulation,2003,108:711-716.
[13]Wolf PA, Mitchell JB, Baker CS. et al. Impact of atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med,1998,158:229-234.
[14]Ringborg A, Nieuwlant R, Lindgren P, et al. Costs of atrial fibrillation in five European countries:results from the Euro Heart Survey on atrial fibrillation. Europace,2008,10: 403-411.
[15]Qi WH. Retrospective investigation of hospitalized patients with atrial fibrillation in ma-inland China. Int J Cardiol,2005,105:283-287.
[16]刘英明,朱智明,曹毅,等.阻断肾素-血管紧张素系统对高血压患者心房颤动发生 危险的影响.中国脏起搏与心电生理杂志,2005,19(4)：264.
[17]LI D, Shinagawa K, Pang L, et al. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing induced congestive heart failure. Circulation,2001,104:2608-2614.
[18]Healey JS, Baranchuk A, Crystal E, et al. Prevention of atrial fibrillation with angio-tensin converting enzyme inhibitors and angiotensin receptor blockers. Journal of the American College of Cardiology,2005,45(11):1832.
[19]Pedersen OD, Bagger H, Kober L, et al. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients wim left ventricular dysfunc-tion. Circulation,1999,100:376-380.
[20]Palardy M, Ducharme A, Nattel S, et al. Absence of protective effect of reninangiotensin system inhibitors on atrial fibrillation development:insights from the Canadian trial of atrial fibrillation (CTAF). Can J Cardiol,2008,24:709-713.
[21]Nakashima H, Kumagai K, Urata H, et al. Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation,2000,101:2612-2617.
[22]Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol, 2003,41:2197-2204.
[23]Akashiba A, Ono H, Ono Y, et al. Valsartan improve LNAME exacerbatedcardiac fibro-sis with TGF-beta inhibition and apoptosis induction inspontaneously hypertensive rats.J cardiol,2008,52:239-246.
[24]刘恩照,李广平,徐昭,李健,杨胜荣,杨万松《中国心脏起搏与心电生理杂志》ISTICPKU-2010年2期
[25]万里燕,崔建,李亮,魏建英,李松鹤.血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗药预防高血压患者房颤发生的Meta分析.《中国药房》2010年第10期.
[26]Disertori M, Latini R, Barlera S, et al. Valsartan for prevention of recurrent atrial fibrilla-tion.N Engl J Med,2009,360:1606-1617
[27]王涛林培林李雅男实用心脑肺血管病杂志2007年9月第15卷第9期
[28]殷跃辉,刘增长,吴近近,等.胺碘酮与氯沙坦、培哚普利联合治疗阵发性心房颤动的前瞻、随机开放研究.中华心血管病杂志,2006,34：299-302.
[29]雷涛,刘小慧,罗太阳,李晖,谷孝艳,陈东,王伟,王海云《心肺血管病杂志》2010年5月.
[30]RobertV,Besse S,Sabri A,et al.Differential regulation of matrix metailoproteinases associated with aging and hypertension in the rat heart, hb Invest,1997, 76:729-738.
[31]Milliez P. Girerd X. Plottin PF, et al. Evidenee for an increase rate of cardiovascular events in patients, ts with primary aldosteromim. J Am Coil Cardiol.2005.45: 1243-1248.
[32]Yang SS, Han W, Zhou HY, et al. Effects of spironolactone on electrical and structural remodeling of atrium in congestive heart failure dogs. Chin Med J (Engl),2008,121: 38-42.
[33]顾磊,王联发,罗骏,周文兵.《中华全科医学》2011年8月第9卷第8期
[34]Shimizu M, Tanaka R, Uchida M, et al. Effect of angiotensin II type 1 receptor blocker on cardiac angiotensin eonverting enzyme and chymase-like activities, and cardiac fibrosis in cardiomyopathic hamsters[J]. J Vet Med Sci,2006,68:227-233.
[35]Lai LP,Su MJ,Lin JL,et al.Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban. J Am Coil of Cardio,1999,33(5):1231.
[36]Yue Li,Feng J,Gaspo R,et al.Ionic remodeling underlying action potential changes in a canine model of Atrial fibrillation. Circ Res,1997,81(4):512-525.
[37]Tieleman RG,De Langen C,Van Gelder IC,et al.Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation,1997,95(7):1945-1950.
[38]Yu WC.Chen SA,Lee SH.Tachycardia-Induced Change of Atrial Refractory Period in Humans:Rate Dependency and Effects of Antiarrhythmic Drugs. Circulation 1998,97 (23):2331-2337.
[39]de Simone A,Stabile QVitale DF,et al.Pretreatment with verapamil inpatients with persis-tent or chronic atrial fibrillation who underwent electrical cardioversion. J Am Coll Cardiol,1999,34(5):810-814.
[40]Fareh S,Benardeau A,Thibault B.The T-Type Ca2+channel blocker mibefradil prevents the development of a substrate for atrial fibrillation by tachycardia-induced atrial remodeling in dogs. Circulation,1999,100(21):2191-2197.