急性心房扩大对兔心房有效不应期的影响及维拉帕米的干预作用

目的:通过建立Langendorff灌流的离体兔心脏模型来研究急性心房扩大对心肌电生理参数及心房颤动(房颤)易感性的影响,了解维拉帕米对其的干预作用。方法:长耳白兔20只建立Langendorff灌流的离体兔心脏模型,随机分为对照组和维拉帕米组。起始右房压力为0,以步长为0.392kPa递增至1.176kPa,在每个压力水平分别测定窦性心动周长(SCL)、心房有效不应期(AERP);应用S1S2刺激评估房颤易感性。结果:随着右房压力由0升高至1.176kPa:(1)对照组AERP显著缩短(P<0.01),且右房压力与AERP呈显著性Spearman负等级相关(rs=-0.664,P<0.01)。(2)对照组S1S2刺激房颤诱发率显著升高(P<0.01)。(3)维拉帕米组不同右房压力水平下心肌各电生理参数及房颤诱发率均无统计学意义(P>0.05)。结论:急性心房扩大使AERP显著缩短,房颤易感性明显提高;维拉帕米可以减弱急性心房扩大对AERP的缩短作用及急性心房扩大对房颤易感性的升高作用。     

丹参酮Ⅱ-A磺酸钠对家兔心房动作电位及快速起搏所致心房电重构的影响

目的研究丹参酮ⅡA磺酸钠(TSN)对家兔在体心房单相动作电位(AMAP)及短期快速心房起搏时电重构的影响,探讨其防治房颤的可能机制。方法家兔24只,随机分为对照组与TSN组各12只。将电极经颈内静脉置入右心房记录AMAP,观察基础状态下、给药后0.5 h及以600次.m in-1心房快速起搏后0.5 h、8 h AMAP及其频率适应性的变化。结果与起搏前相比对照组AERP200 m s在起搏后0.5h缩短21.2 m s,起博后8h缩短21.6m s(P<0.05),且心房肌的频率适应性丧失。TSN在基础状态下对AMAPA、AMAPD无明显影响,但使AERP200 m s由(105.9±3.8)m s延长至(114.7±7.2)m s(P<0.05)。起搏后TSN组维持原有的心房肌频率适应性。结论快速心房起搏使心房肌的频率适应性丧失而致电重构,TSN能通过抑制L-型钙通道减轻短期快速心房起搏所致电重构。     

晚钠电流抑制剂雷诺嗪对犬急性心房电重构的影响

目的探讨晚钠电流抑制剂对犬急性心房电重构的影响。方法选择性晚钠电流抑制剂雷诺嗪在 24只犬中建立急性心房电重构模型并采用随机数字表法分为低、中、高剂量组,与对照组比较房颤持续时间、心房有效不应期( AERP)、房颤诱发率等变化。结果三个剂量组较对照组的房颤持续时间是下降但差异无统计学意义( F＝1.95,P＝0.154);与对照组相比,三个剂量组的房颤诱发率均明显下降,差异有统计学意义( χ2＝53.25,P＜0.01)其中低剂量组( 53.4%比 74.3%)中剂量组(41.6%比 74.3%),高剂量组( 34.0%比 74.3%)。三个剂量组所测的 ERP较对照延长,差异有统计学意义( P＜0)。结论组,.05,雷诺嗪可通过减弱晚钠电流可以明显改善急性心房电重构并抑制房颤的诱发。     

高频刺激右心耳引起家兔慢性心房颤动

目的 探讨以高频率起搏刺激右心耳建立家兔慢性心房颤动模型的方法.方法 20只家兔随机分为实验组及对照组,对照组为假手术组.植入起搏电极但不起搏;实验组10只家兔予开胸植入双极电极并予以(800次/min)刺激右心耳30d,4h/d,术后定期监测起搏、心房颤动的发生情况,同时测定起搏前及房颤发生后心房有效不应期(AERP)的变化.结果 实验组均完成了实验,术后第7d,7只(70%),兔发生了房颤,2周时共有8只(80%)发生了房颤并能稳定维持(与对照组比较,P<0.01),30 d时仍示房颤,其余2只兔至30d时仍呈起搏心律;对照组则未发生任何心律失常情况.AERP缩短,AERP频率适应不良,与基础状态相比有显著意义.结论 长期高频率起搏刺激家兔右心耳是建立慢性房颤模型的有效方法.     

氯沙坦对急性心房颤动心房肌L型钙离子通道的影响

目的探讨氯沙坦对家兔急性心房颤动模型的心房肌L型钙离子通道的影响。方法家兔30只随机分为0．9％氯化钠溶液起搏（NSP）组、氟沙坦起搏（LP）组。观测每组基础状态、快速心房起搏时心房有效不应期（AERP）及心房肌L-型钙通道的电流密度（ICa-L）进行统计学处理。结果快速起搏8h后NSP组AERP的下降较LP组显著,差异有统计学意义（P〈0．05）;LP组较NSP组心房肌ICa-L差异无统计学意义（P〉0．05）;但其标准差显著降低（P〈0．05）。结论氯沙坦可以抑制快速心房起搏引起AERP缩短及心房肌ICa-L离散度增加,从而减轻心房颤动（AF）的电重构。     

蝙蝠葛碱对家兔急性房颤连接蛋白40重构的影响及其机制

目的　观察快速心房起搏所致急性心房颤动 (房颤 )对家兔心房肌组织Ca2 + 含量和连接蛋白 4 0 (Connexin 4 0 ,Cx4 0 )重构的影响以及钙通道阻滞剂蝙蝠葛碱 (DAU)的干预作用 ,并对其作用机制进行探讨。方法　 32只家兔随机分为 3组 :对照组 (n =8)、房颤组 (n =12 )、DAU组 (n =12 )。经颈内静脉将电极置入右心房 ,对照组不予心房起搏 ,另外两组以 6 0 0beat·min-1行快速心房起搏以诱发房颤 ,并且DAU组于快速起搏前 30min按 5mg·kg-1静脉给予DAU ,其余两组则给予等量的生理盐水。用生化方法检测右心耳组织Ca2 + 含量 ,并分别用Westernblot和免疫荧光标记激光共聚焦显微镜检测Cx4 0的含量和分布。结果　房颤组心房组织Ca2 + 含量高于对照组 ,Cx4 0含量低于对照组 (P均 <0 0 1) ,房颤组Cx4 0分布不均一 ;蝙蝠葛碱组Ca2 + 、Cx4 0含量分别低于和高于房颤组 (P均 <0 0 5 ) ,Cx4 0分布不均一的程度较房颤组减轻。结论　快速心房起搏诱发急性房颤可引起家兔心房肌Ca2 + 含量升高、Cx4 0含量降低和分布不均一 ,蝙蝠葛碱能有效抑制Ca2 + 含量升高、减轻Cx4 0重构 ,钙超载可能参与房颤Cx4 0重构。     

心房不同部位起搏对阵发房颤患者心房激动时间的影响

目的　比较右心耳 (RAA)、冠状窦远端 (DCS)、右房双部位 (右心耳加冠状窦口 ,DSA)和双房 (右心耳加冠状窦远端 ,BiA)起搏对阵发房颤 (PAf)患者心房激动时间的影响。方法 2 2例接受心脏电生理评价试验的PAf患者在窦性心律下行心房不同部位起搏 ,同步记录 12 -导心电图 ,测量最大P波时限。结果与窦性P波时限相比 ,RAA起搏明显延长P波时限 (P <0 0 1) ,DCS、DSA及BiA起搏则明显缩短P波时限 (P <0 0 1)结论DCS、DSA及BiA起搏明显缩短心房激动时间 ,减少心房电活动的离散度 ,有利于PAf的防治     

阵发性房颤诱发大鼠心房肌电重构特征研究

目的:探讨氯化钙-乙酰胆碱混合液引起的房颤大鼠心房电重构特征。方法:雄性SD大鼠,随机分为正常组和模型组,每组20只。CaCl210mg/mL+ACh 66μg/mL混合液尾静脉注射诱发大鼠房颤,连续诱发7d,正常组静脉注射生理盐水7d。心电图监测大鼠房颤持续时间、心房复极相关心电图参数变化。7d后,观察正常和房颤大鼠心房肌有效不应期,Western-blot法测定心房肌通道蛋白Kv 1.5、Kv 4.2/4.3,钙稳蛋白FKBP 12.6和缝隙连接蛋白Cx40的表达。结果:Ach-CaCl2连续静脉注射引起大鼠房颤持续时间逐渐延长,与正常组相比,房颤大鼠P波变宽,Pd增大,心房有效不应期缩短(P<0.01),同时心房肌Kv 1.5、Kv 4.2/4.3表达下降,FKBP12.6减少,Cx40含量下降(P<0.05)。结论:氯化钙-乙酰胆碱混合液持续给予7d,大鼠心房发生电重构,特征符合或接近临床房颤基质电重构特征。     

胺碘酮联合厄贝沙坦治疗阵发性心房颤动疗效观察

目的观察胺碘酮联合厄贝沙坦治疗阵发性房颤的疗效。方法选择2008年5月～2010年5月期间该院83例阵发性房颤患者,随机分为治疗组(胺碘酮+厄贝沙坦)和对照组(单用胺碘酮),疗程均为一年。结果治疗组窦性心率维持率明显高于对照组(P<0.05),左房内径亦有显著性缩小(P<0.05)。结论厄贝沙坦具有抑制心房电重构和解剖重构,降低房颤复发率及阻止房颤持续的作用,胺碘酮联合厄贝沙坦治疗阵发性心房颤动维持窦性心率的疗效优于单用胺碘酮,且能抑制左房扩大。     

右美托咪定对快速心房起搏后兔心房电生理学特性及Cx43 Cx40表达的影响

目的 探讨右美托咪定对快速心房起搏后兔心房电生理学特性及Cx43、Cx40表达的影响。方法 选择成年雄兔24只,随机分为对照组（C组）、快速心房起搏组（RAP组）与快速心房起搏+右美托咪定灌流组（RAP+DEX组）,每组8只。制备Langendorff离体心脏灌注模型,通过快速心房起搏构建房颤模型。分别检测3组心房90%单相动作电位复极时程（MAPD₉₀）、心房有效不应期（ERP）、ERP与MAPD₉₀比值（ERP/MAPD₉₀）、房颤诱发率及持续时间,取心房组织,采用Western-bolt法和免疫荧光法检测Cx43、Cx40的蛋白含量和分布。结果 T₁~T₃时,3组MAPD₉₀比较,差异有统计学意义（P<0.05）。RAP组MAPD₉₀随时间的推移有逐渐下降趋势（P<0.05）,不同的处理方式和时间对MAPD₉₀有交互作用（P<0.05）。T₃时,RAP组ERP、ERP/MAPD₉₀、Cx43和Cx40蛋白含量均低于C组和RAP+DEX组,房颤诱发率高于C组和RAP+DEX组,差异有统计学意义（P<0.05）。3组房颤持续时间比较,差异无统计学意义（P>0.05）。电镜下,RAP组Cx43和Cx40分布不规律且侧面分布增多,而C组和RAP+DEX组Cx43和Cx40分布较规律且主要集中在两端。结论 右美托咪定可抑制房颤时的心房电重构,降低房颤的易感性,其机制可能与其抑制Cx43、Cx40的表达下调和再分布有关。     

Effects of spironolactone on atrial structural remodelling in a canine model of atrial fibrillation produced by prolonged atrial pacing

Background and purpose:

Suppression of the renin-angiotensin-aldosterone system can prevent atrial fibrillation (AF) by attenuating atrial structural remodelling but the role of aldosterone in AF prevention has not been investigated thoroughly. We explored whether the aldosterone antagonist, spironolactone, could improve atrial structural remodelling in long-term rapid pacing-induced AF.

Experimental approach:

Three groups of dogs were used, sham-operated, control and spironolactone-treated groups. Dogs in the control and spironolactone groups had right atrial pacing for 6 weeks. The spironolactone group was given spironolactone 1 week before and during the atrial pacing. After 6 weeks of pacing, atrial structural and functional changes were assessed by echocardiography, haemodynamic parameters by cardiac catheterization, histopathological changes by light and electron microscopy and cardiomyocyte apoptosis by TUNEL. Caspase-3, Bcl-2, bax, calpain I, calpastatin, matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase (TIMP)-1 were analysed by immunohistochemistry and Western blotting. The inducibility and duration of AF were measured by atrial burst pacing.

Key results:

After atrial pacing, the proportion of TUNEL positive cells, myolysis, atrial fibrosis and dilatation were all significantly increased and these changes were inhibited by spironolactone. Spironolactone treatment reversed the increased expression of caspase-3, bax, calpain I and MMP-9 and the decreased level of Bcl-2, calpastatin and TIMP-1, induced by chronic atrial pacing. Also spironolactone prevented the increased inducibility and duration of AF, induced by tachypacing.

Conclusions and implications:

Treatment with spironolactone prevented myocardial apoptosis, myolysis, atrial fibrosis and dilatation, suggesting a possible beneficial effect of aldosterone antagonism on atrial structural remodelling in AF.This article is commented on by Lendeckel et al., pp. 1581–1583 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00675.x     

n-3 (omega-3) polyunsaturated fatty acids prevent acute atrial electrophysiological remodeling

BACKGROUND AND PURPOSE: Recent reports suggest that n-3 (omega-3) polyunsaturated fatty acids (PUFAs) may reduce atrial fibrillation (AF). Reduction of the atrial effective refractory period (ERP) is believed to be an important early remodeling event that favors the development and perpetuation of AF. We hypothesized that n-3 PUFAs would attenuate early atrial electrophysiolgical remodeling in a canine model of acute atrial tachypacing. EXPERIMENTAL APPROACH: Adult dogs of either sex received n-3 PUFAs (n=6), n-6 PUFAs (n=6), or saline (n=6) infused over 1 h. After a stable ERP was established, treatment was initiated concurrently with 6 h of rapid atrial pacing (400 b.p.m.). Serial right atrial ERPs were measured during rapid atrial pacing, and induction of atrial tachyarrhythmias was attempted at the conclusion of each study. KEY RESULTS: There was no change in P wave duration or in the PQ, QRS, QT or QTc intervals in any of the treatment groups. N-3 PUFA treatment significantly reduced the shortening of atrial ERP, compared to both control groups (P<0.05). In separate experiments, the same n-3 PUFA infusion was given to dogs remaining in normal sinus rhythm. During sinus rhythm, n-3 PUFA infusion did not alter any electrocardiogram (ECG) parameter or the atrial ERP. CONCLUSIONS AND IMPLICATIONS: We conclude that acute n-3 PUFA treatment prevents acute atrial electrophysiological remodeling during high rate activity, which may minimize the self-perpetuation of AF.     

慢性心房颤动犬心房组织肾素-血管紧张素系统的表达及意义

目的探讨肾素-血管紧张素系统(RAS)在慢性心房颤动犬心房组织中的表达及意义。方法健康杂种犬16条,随机分为正常对照组8条,单纯心房颤动起搏组8条。心房颤动组植入埋藏式高频率心脏起博器(500±20)次/min,起博24周后处死动物,分别于左、右心房取材,采用免疫组织化学检测心房组织中肾素-血管紧张素转化酶(ACE)、血管紧张素Ⅱ1型受体(AT1R)以及肾素-血管紧张素转化酶抑制剂(ACEI)的表达变化。正常对照组未植入起搏器,与心房颤动组同步行相应检查。结果与对照组比较,心房颤动组心房组织中ACE和AT1R表达水平显著增强,而ACEI的表达水平明显下降,各组间比较差异有统计学意义(P<0.01)。结论慢性心房颤动犬心房组织RAS的激活参与了心房颤动的形成,可能是心房颤动发生、发展的主要机制之一。     

Effects of a new class III antiarrhythmic drug nibentan in a canine model of vagally mediated atrial fibrillation

Nibentan, a new class III antiarrhythmic drug, is highly effective in patients with atrial flutter and fibrillation. However, its mechanism of action remains unclear. The aim of this study was to investigate the effects of nibentan using a canine model of vagally sustained atrial fibrillation (AF). Nibentan was intravenously infused to anesthetized open-chest dogs during vagally induced AF. Cumulative doses of nibentan (0.063, 0.125, and 0.250 mg/kg) successfully terminated AF in 78, 88, and 100% as well as prevented AF reinduction in 11, 63, and 90% of cases, respectively. All doses of nibentan significantly and rate-independently increased atrial effective refractory period (AERP) with and without vagal stimulation. Activation mapping (224 epicardial electrodes) during AF showed that nibentan reduced the number of simultaneously occurring reentrant wavelets. Herewith the atrial excitation slowed down until conduction failure of reentrant wavelets led to arrhythmia termination. These changes in activation patterns can be accounted for by nibentan-induced increase of AERP (55 +/- 9%, 82 +/- 12%, and 90 +/- 6%; p < 0.01) and wavelength for reentry (47 +/- 7%, 68 +/- 12%, and 72 +/- 4%; p < 0.01) at rapid atrial rates in the presence of vagal stimulation. In conclusion, the high efficacy of nibentan against AF was associated with significant rate-independent increase in AERP and in wavelength, and might be in part explained by block of both delayed rectifier (I(K)) and muscarinic I(K,ACh) currents.     

Effect of amiodarone on dispersion of ventricular repolarization in a canine congestive heart failure model

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Effects of a novel amiodarone-like compound SAR114646A on the pig atrium and susceptibility to ventricular fibrillation in dogs and pigs

Amiodarone is one of the most effective antiarrhythmic drugs. However, poor solubility of this compound has limited its intravenous application. SAR11464A is a water-soluble amiodarone-like drug that lacks iodine and inhibits multiple cardiac ion channels in vitro. This study evaluated the antiarrhythmic efficacy of this drug in vivo. In porcine studies, atrial effective refractory period (AERP) was measured in pentobarbital-anesthetized thoracotomized pigs and atrial fibrillation (AF) was induced by a premature beat. Ventricular fibrillation (VF) was induced via either burst pacing or programmed electrical stimulation (a series of progressively shorter beats, S1–S5). In canine studies, VF was induced by a 2-min occlusion of the left circumflex coronary artery during the last minute of exercise in dogs with healed myocardial infarctions (n = 8). One week later, this test was repeated after pretreatment with SAR114646A (3.0 mg/kg, i.v., slow bolus). SAR114646A produced a significant dose-dependent prolongation of AERP, inhibited AF induced by a premature stimulus, and electrically induced VF in anesthetized pigs. At 1.0 and 3.0 mg/kg, i.v., it was superior to amiodarone, dofetilide, and flecainide. In dogs, SAR114646A did not alter any ECG parameter including QTc (control, 236.9 ± 8.5 ms vs. SAR, 237.2 ± 3.5 ms) but significantly reduced the incidence of VF, protecting six of eight animals (Fisher’s exact test, P = 0.01). SAR114646A was effective against both atrial and ventricular arrhythmias without altering ventricular repolarization. These data suggest that the amiodarone-like drug SAR114646A may be an effective antiarrhythmic intervention that does not adversely prolong ventricular repolarization.     

Current Management of Symptomatic Atrial Fibrillation

Atrial fibrillation (AF) is the most commonly encountered sustained arrhythmia. Heart rate control, reduction of symptoms, and prevention of embolism are major goals of treatment. Whether the strategy of cardioversion with subsequent maintenance of sinus rhythm has an advantage over heart rate control is under active investigation. Digoxin, non-dihydropyridine calcium channel antagonists, β-adrenoceptor antagonists (β-blockers), and amiodarone are the pharmacologic agents most commonly used to achieve rate control. In patients with drug-resistant AF, atrioventricular nodal ablation (or modification) with implantation of a permanent pacemaker is an alternative therapy. Conversion to sinus rhythm can best be achieved by electrical cardioversion. In selected patients, pharmacologic cardioversion can also be attempted. The use of antiarrhythmic drugs for the maintenance of sinus rhythm depends on several factors: (i) the nature of the arrhythmia (first attack, paroxysmal AF with frequent attacks, paroxysmal AF with infrequent attacks, or persistent AF); (ii) the associated symptoms; and (iii) the risk of severe adverse effects associated with the chosen drug. If the administration of an antiarrhythmic drug is appropriate, the choice of the drug must be tailored to the specific characteristics of the given patient. In lone AF, class Ic antiarrhythmic drugs are the best tolerated. These agents should be combined with a calcium channel antagonist or a β-blocker to prevent rapid ventricular response in the case of conversion of AF to atrial flutter. In this situation, catheter ablation of atrial flutter at the isthmus (hybrid therapy) should be performed. All class I antiarrhythmic agents should be avoided in patients with structural heart disease. Alternative approaches that may be used if sinus rhythm cannot be maintained with drug therapy include: (i) the ablation of arrhyth-mogenic pulmonary veins; (ii) the implantation of an atrial defibrillator; (iii) the use of specific pacing sites; or (iv) pacing modes. Whether these approaches will reach clinical relevance merits further investigation. Intraoperative catheter ablation or surgical ablation (maze procedure) seems a promising approach for curing AF in patients undergoing cardiac surgery. Among all of the available treatment options, the most consistent proof of efficacy in reducing mortality and morbidity from AF exists for antithrombotic treatment.     

关白附总碱盐抗大鼠房颤作用

目的观察关白附总碱盐抗房颤作用。方法雄性SD大鼠,随机分组,CaCl210mg/mL+ACh 66μg/mL混合液iv诱发大鼠房颤,连续7d,于大鼠造模第4天起,关白附治疗组po 5、15、45mg/kg,绝奈达隆1mg/kg ip,每天1次,正常组静脉注射生理盐水7d。心电图监测大鼠房颤持续时间及QTc。7d后,测定大鼠心房肌有效不应期,western-blot法测定心房肌缝隙连接蛋白Cx40的表达。结果 Ach-CaCl2连续静脉注射引起大鼠房颤持续时间逐渐延长,与正常组比,心房有效不应期缩短(P<0.01),心房肌Cx40含量下降(P<0.05)。关白附能有效抑制房颤持续时间,延长心房ERP,保护心房Cx40表达。结论关白附能有效对抗房颤,改善房颤引起的电重构。