辛伐他汀对老年犬急性心房电重构的影响

目的通过快速心房起搏(ATP)建立犬心房心动过速心房重构模型,观察辛伐他汀对急性心房电重构的影响,探讨辛伐他汀防治心房颤动(AF)的作用机制。方法健康成年杂种犬21只(雌雄不拘,体重10¹2.5 kg)。随机分为三组:对照组ATP组、药物干预组。药物干预组起搏前5 d给予辛伐他汀20 mg/d口服。右侧开胸将电极置于右心耳及右心房侧壁。ATP组和药物干预组以480次/min的频率快速起搏右心房,于实验开始及起搏后6 h对每只犬进行非开放性电生理检查,测定心房有效不应期(AERP)及burst刺激诱发AF频率和AF持续时间。结果对照组在整个时间内AERP无变化。ATP组ATP后,AERP明显缩短。药物干预组ATP后AERP亦缩短,但较ATP组变化明显减轻。各组起搏前AF的频率和持续时间没有差异。对照组在手术前后AF的频率和持续时间无变化。ATP组ATP后AF的诱发频率明显增多和持续时间延长。药物干预组与ATP组比较AF诱发频率及持续时间明显得到抑制。结论心房电重构造成的AERP等电生理变化促进了AF发生和维持。辛伐他汀对ATP引起的犬急性心房电重构具有一定的预防作用,并能削弱ATP对犬AF的促发作用。     

心房颤动电重构的实验研究

目的 :研究犬心房颤动 (Af)模型心房有效不应期 (ERP)的变化 ,验证Af电重构这一假说的正确性。方法 :采用快速心房起搏的方法建立犬的Af模型 (起搏组 ,n =13) ,用程序刺激测量心房的ERP ;观察P波时限和PA间期的变化 ,并与假手术组 (对照组 ,n =7)作比较。结果 :持续快速起搏 9～ 10周后 ,心房ERP明显缩短 ,当S1S1为 30 0ms时 ,对照组与起搏组分别为 (15 0± 2 1)ms与 (115± 2 3)ms(P<0 .0 1) ;S1S1为 4 0 0ms时分别为(15 4± 2 4 )ms与 (10 5± 2 7)ms(P <0 .0 1)。起搏组P波时限和PA间期明显长于对照组。结论 :持续心房快速刺激可使ERP明显缩短 ,使心房发生电重构。心房电重构可促进Af的发生和发展     

心房有效不应期离散度与心房颤动

心房颤动是临床最常见的心律失常之一,有较高的致残率及致死率,关于心房颤动的机制有较多的学说,目前研究已经证实心房电重构能够促进心房颤动的发生与维持,心房电重构包括心房有效不应期的缩短,心房有效不应期离散度的增加及局部电传导的减慢,现就心房有效不应期离散度与心房颤动的关系及其影响机制做一综述。     

短时间快速右心房起搏致犬心房电重构、收缩重构及解剖重构的实验研究

目的通过对快速心房起搏犬的电生理特性、收缩功能及超微结构的研究,观察短时间快速心房电活动是否可引起心房重构,并探讨其在房颤持续中的作用。方法健康杂种犬17只。实验组12只,经右心耳起搏450次／min,持续5小时。快速心房刺激前后分别测量P波时程及心房有效不应期,并用多普勒超声评价二尖瓣前向血流变化。实验结束后取左心耳及梳状肌组织观察其超微结构。对照组5只,插入电极但不起搏,与实验组同步行各项检查。结果持续快速刺激5小时后,实验组心房有效不应期降低,P波时程增加;二尖瓣心房收缩期血流速度降低了17％;检查发现部分心肌细胞出现肌原纤维的损失、糖原累积及线粒体大小及形状的改变;而对照组均未发现明显变化。结论短时间快速心房电活动可导致犬心房发生电重构、收缩重构及结构重构,而心房结构重构可能是心房发生电重构和收缩重构的原因之一。     

肺静脉电隔离对犬急性心房电重构影响的实验研究

目的肺静脉电隔离（PVI）是治疗心房颤动（房颤）的重要手段，心房电重构是房颤发生和维持的重要因素。本研究旨在研究PVI对急性心房电重构的影响并揭示其可能机制。方法选取成年杂种犬18只，随机分为对照组和PVI组。应用硫代巴比妥钠麻醉后分离并结扎双侧颈交感迷走神经干。两组犬均行房间隔穿刺并以600次／min起搏右心房30min构建急性心房电重构模型，PVI组穿间隔后即行环肺静脉口部电隔离。快速心房电刺激前后于右心耳（RAA）及左心耳（LAA）处测量基础状态下（非迷走神经刺激）及颈部迷走神经干刺激时的心房有效不应期（ERP）和房颤易感窗口（VW）。结果（1）对照组快速心房电刺激后基础状态下（RAA处P〈0．01，LAA处P〈0．001）和迷走神经刺激时（RAA处P〈0．05，LAA处P〈0．05）测得的ERP均明显缩短。快速心房电刺激前后基础状态下均不能诱发房颤；快速心房电刺激后，RAA（P〈0．01）和LAA处（P〈0．05）的VW在迷走神经刺激时明显增宽。（2）PVI组快速心房电刺激后基础状态下（RAA处P=0．451，LAA处P=0．197）和迷走神经刺激时（RAA处P=0．104，LAA处P=0．231）测得的ERP较快速心房电刺激前无明显变化。快速心房电刺激前后基础及迷走神经刺激下均不能诱发房颤。（3）对照组快速心房电刺激后ERP缩短值较PVI组明显增加（基础状态时LAA处P〈0．05，RAA处P〈0．05；迷走神经刺激时LAA处P〈0．01，RAA处P〈0．05）。结论心房电重构伴随着迷走神经对心房电生理特性调节活动增强，肺静脉电隔离能减轻心房电重构，其机制可能为心房去迷走神经效应。     

心房颤动引起心房电重构机制的研究进展

1　引言心房颤动 (简称房颤 )能引起心房电生理功能的改变 ,促使房颤的发生和维持 ,这一过程通常称之为“心房电生理重构”(简称电重构 )。电重构是 1995年由Wijffels等提出 [1]。他们给山羊安装一种起搏装置 ,通过对两心房的超速起搏 (>4 0 0次 /分 [BPM]) ,发现超速起搏可诱发房颤 ,而且随着刺激时间的延长 ,房颤的持续时间也延长 ,这就是“房颤致房颤”理论的来源。很久以前临床医生就发现房颤的自然病程常由自发性向持续性转变 ,暗示了房颤的发生能改变心房特性 ,从而增加了持续心律失常的可能性 ,Wijffels等称之为“房颤的驯化”(Do…     

快速刺激及药物对犬肺静脉电重构的影响研究

目的研究快速刺激及药物（维拉帕米、阿托品）刺激对犬肺静脉电重构的影响,探讨肺静脉对心房颤动（房颤）的发生及维持的作用。方法测量快速刺激及药物（维拉帕米、阿托品）刺激犬肺静脉时肺静脉有效不应期、有效不应期频率适应性、房颤诱发率和持续时间。结果①与刺激前比较．快速刺激时肺静脉有效不应期及有效不应期频率适应性在刺激后即刻、5min有显著性差异．刺激后10min时无明显差异;刺激前、后肺静脉的房颤诱发率及房颤持续时间有显著性差异。②维拉帕米、阿托品使肺静脉有效不应期缩短及有效不应期频率适应性下降。结论快速刺激犬肺静脉可以导致肺静脉发生急性电重构．但可在短时间内恢复。在犬的试验中维拉帕米、阿托品可改变肺静脉发生电重构的程度,并加快肺静脉有效不应期频率适应性恢复速度。     

快速刺激及药物对犬肺静脉电重构的影响研究

目的 研究快速刺激及药物(维拉帕米、阿托品)刺激对犬肺静脉电重构的影响,探讨肺静脉对心房颤动(房颤)的发生及维持的作用.方法 测量快速刺激及药物(维拉帕米、阿托品)刺激犬肺静脉时肺静脉有效不应期、有效不应期频率适应性、房颤诱发率和持续时间.结果 ①与刺激前比较,快速刺激时肺静脉有效不应期及有效不应期频率适应性在刺激后即刻、5 min有显著性差异,刺激后10 min时无明显差异;刺激前、后肺静脉的房颤诱发率及房颤持续时间有显著性差异.②维拉帕米、阿托品使肺静脉有效不应期缩短及有效不应期频率适应性下降.结论 快速刺激犬肺静脉可以导致肺静脉发生急性电重构,但可在短时间内恢复.在犬的试验中维拉帕米、阿托品可改变肺静脉发生电重构的程度.并加快肺静脉有效不应期频率适应性恢复速度.     

氯沙坦对心房急性电重构的影响

目的　以地尔硫为对照 ,探讨氯沙坦对心房快速起搏诱发急性电重构的干预作用。方法　 2 1只兔随机分为盐水组、地尔硫组和氯沙坦组。 2F电极导管分别置于高位右心房 (HRA)、低位右心房 (LRA)和希氏束区 (HIS) ,以最快 1∶1起搏频率心房起搏 3h。阻断自主神经后 ,观察各组心房快速起搏前后 ,不同部位心房有效不应期 (AERP)、AERP频率适应性、AERP离散度 (AERPd)及右心房内传导时间变化。结果　 (1)心房快速起搏后 ,盐水组AERP2 0 0 和AERP150 立即缩短 ;起搏 1h达最小值(P <0 0 5 ) ,起搏 0 5h内AERP2 0 0 和AERP150 缩短速率最快 [(30 2± 10 5 )ms/h ,(2 4 1± 9 1)ms/h];地尔硫组和氯沙坦组心房快速起搏后AERP无显著缩短。 (2 )心房快速起搏前 ,盐水组HRA处(AERP2 0 0 -AERP150 ) / 5 0ms为 0 17± 0 0 8,起搏 0 5、1、2、3h后分别为 0 0 8± 0 0 6、0 0 9± 0 0 6、0 0 8± 0 0 4、0 0 9± 0 0 5 ,P <0 0 5 ,提示AERP频率适应性降低 ;地尔硫组和氯沙坦组心房快速起搏前后 ,该值差异无显著性。 (3)盐水组心房快速起搏 2、3h ,AERPd明显增大 (P <0 0 5 )。地尔硫组心房快速起搏 3h ,与起搏前比较 ,AERPd显著增大 (P <0 0 5 )。氯沙坦组心房快速起搏后 ,AERPd无显著增加。     

Contribution of mi RNAs to ion-channel remodelling in atrial fibrillation

Atrial fibrillation(AF) is the most commonly encountered clinical arrhythmia associated with pronounced mortality and morbidity, which are related to palpitations, fainting, congestive heart failure, and stroke. Prolonged episodes of AF promote AF persistence mainly due to electrical remodelling that alters ion-channel expression and/or function. Micro RNAs(mi RNAs), a new class of noncoding mR NAs of around 22 nucleotides in length, have recently emerged as one of the key players in the geneexpression regulatory networks. The potential roles of miR NAs in controlling AF have recently been investigated. Several recent studies have provided promising results for a better understanding of the molecular mechanisms of AF. In this review, we summarize the mechanism of miR NAs as regulators of ion-channel gene expression and their role in causing AF through electrical remodelling.     

盐酸关附甲素在犬迷走神经性心房颤动模型中的作用

目的研究盐酸关附甲素终止心房颤动(简称房颤)的疗效,并探讨其抗心律失常作用的机制。方法30只杂种犬,在刺激双侧迷走神经的基础上给予快速心房刺激诱发房颤,随机分为生理盐水对照组、盐酸关附甲素低剂量组(15mg/kg)和高剂量组(22.5mg/kg)。观察盐酸关附甲素终止房颤和预防房颤再诱发的作用,以及对心房电生理指标的影响。结果对照组仅1只房颤终止;盐酸关附甲素低剂量组共9只房颤终止,均在注射第一剂药物后(P<0.01);高剂量组共8只房颤终止,7只在第一剂药物注射后,1只在第二剂药物注射后(P<0.01);盐酸关附甲素两个剂量组均显著延长心房不应期30ms以上;两个剂量均延长窦性周长、P波时限、PR间期、PR段、QT间期、QT-c间期、JT间期;盐酸关附甲素可预防房颤再诱发,低剂量组有6只,高剂量组有5只,均明显高于对照组(P<0.01)。结论盐酸关附甲素能够终止房颤,总有效率达87.5%,显著延长心房有效不应期可能是其抗心律失常作用机制之一;盐酸关附甲素可预防房颤再次诱发,有效率达50%以上。     

Attenuation of electrical remodelling in chronic atrial fibrillation following oral treatment with verapamil.

AIMS: Electrical remodelling with shortening of the atrial refractory period and increased fibrillatory rate occurs after onset of atrial fibrillation and can be attenuated by pre-treatment with intravenous verapamil. The aim of the present study was to investigate whether already established fibrillatory-induced shortening of atrial fibrillatory cycle length could be reversed with oral verapamil. METHODS AND RESULTS: Thirteen patients (nine men; mean age 67 years) with chronic atrial fibrillation (CAF) were studied. The dominant atrial cycle length (DACL) was estimated non-invasively using the frequency analysis of fibrillatory ECG (FAF-ECG) method. Measurements were repeated following treatment with slow release oral verapamil. DACL increased from 147 +/- 13 ms to 156 +/- 21 ms after 1 day (P=0.02), to 164 +/- 18 ms after 5 days (P=0.005) and finally to 160 +/- 16 ms after 6 weeks (P=0.008). CONCLUSION: Long-term oral treatment with verapamil increases the DACL significantly in patients with CAF. The prolongation is evident after 1 day and is further developed during the first 5 days of treatment. Since DACL is believed to be an index of refractoriness, the findings of the present study suggest that this treatment increases the atrial refractory period in patients with CAF.     

The effect of endocardial defibrillator shocks on basic atrial electrophysiology in man. Is post cardioversion atrial electrical 'remodelling' artefact?

AIMS: To determine the effect of an endocardial DC shock on the basic electrophysiology of the human atrium if delivered in sinus rhythm. METHODS AND RESULTS: A 5J endocardial R wave synchronized DC shock was delivered in 10 patients in stable sinus rhythm during ICD implantation for ventricular arrhythmias. There was no prior history of atrial fibrillation. Monophasic action potential duration (APD) and atrial effective refractory periods (AERP) were evaluated before, 1 min post DC shock, and 15 min post shock. These parameters were assessed at basic cycle lengths and at atrial paced cycle lengths of 600 ms and 400 ms at two right atrial sites; mid lateral right atrial wall (MRLA) and the right atrial appendage (RAA). There were no significant differences in APD 90, AERP or atrial refractory dispersion at any site or drive cycle length before, immediately after or 15 min after shock delivery. CONCLUSIONS: There are no significant changes in basic electrophysiological parameters following a DC shock delivered in sinus rhythm in patients with no prior history of atrial fibrillation. This suggests that atrial electrical remodelling occurs as a result of atrial fibrillation and is unrelated to shock artefact.     

Amyloid deposition as a cause of atrial remodelling in persistent valvular atrial fibrillation.

AIM: The spectrum of histological alterations, namely atrial amyloidosis, in the right and left atria of patients with chronic persistent atrial fibrillation (AF) and rheumatic heart disease is not completely known. METHODS AND RESULTS: One hundred and twenty-eight atrial appendages (66 left and 62 right), obtained from 72 patients with rheumatic valve disease and chronic AF undergoing cardiac surgery for valve replacement or repair and AF treatment were histologically evaluated for the presence of amyloid deposits. One hundred and four specimens of left and right auricles from 52 patients in sinus rhythm with severe chronic heart failure undergoing heart transplant were also analyzed (controls). Amyloid was found in 33 (46%) valvular patients with chronic persistent AF and in 6 (12%) controls. Amyloid was related to the presence and duration of AF, was more frequently found in left atrial samples and was independent of age. On stepwise logistic regression analysis, AF duration and female gender were independently related to amyloid deposition. CONCLUSIONS: Patients with long-standing AF and rheumatic heart disease have a very high prevalence of atrial amyloidosis. Amyloid deposition is more frequent in left than in right atrial appendage and correlates with AF duration and female gender. Amyloid deposition could constitute an additional histological feature in the structural remodeling of atria during long-standing AF, at least in rheumatic valve disease. Persistence of AF might play a pivotal role in promoting amyloid deposition.     

Role of dispersion of atrial refractoriness in the recurrence of clinical atrial fibrillation; a manifestation of atrial electrical remodelling in humans?

AIMS: The mechanism of atrial fibrillation recurrence following cardioversion is unknown, although experimental studies have indicated that changes in dispersion of atrial refractoriness may play a role. The aims of this study were to assess (1) if dispersion of atrial refractoriness is relevant to atrial fibrillation recurrence and (2) if dispersion of refractoriness is part of the atrial electrical remodelling process in humans. METHODS AND RESULTS: Thirty-seven consecutive patients underwent internal cardioversion (CV1) of persistent atrial fibrillation. Patients were monitored by daily transtelephonic recordings following discharge and if there was spontaneous atrial fibrillation recurrence they were rapidly admitted for repeat cardioversion (CV2). We used the 5th percentile of 100 consecutive atrial fibrillation cycle lengths (AFCL(P5)) and the atrial effective refractory period (AERP) as measures of atrial refractoriness at four different atrial sites. Dispersion of AFCL(P5)at CV1 was significantly higher in those who had subsequent recurrence of atrial fibrillation than in those who remained in sinus rhythm for at least 1 month after cardioversion (35+/-17 ms vs 9+/-13 ms;P<0.02). Dispersion of AFCL(P5)measured at CV2 was significantly lower than that measured in the same patients at CV1 (19+/-8 ms vs 35+/-11 ms;P=0.02). i.e. dispersion of AFCL(P5)had reduced following a period of sinus rhythm. In contrast, there was no difference in dispersion of AERP between the recurrers and non-recurrers. Dispersion of AERP between CV1 and CV2 did not change following a period of sinus rhythm. CONCLUSION: Dispersion of AFCL is relevant to atrial fibrillation recurrence and may represent a manifestation of atrial electrical remodelling in humans. Treatment directed at AFCL dispersion may be useful in the suppression of atrial fibrillation recurrence following cardioversion.     

依那普利对心房急性电重构影响的临床研究

目的　探讨依那普利对快速心房起搏诱发心房急性电重构的干预作用。方法　 2 7例阵发性室上性心动过速行射频消融术患者随机分为对照组 ( 16例 )和依那普利组 ( 11例 )。阻断自主神经后 ,以最快 1:1心房起搏 [( 349± 37) /min]诱发急性心房颤动 (房颤 ) ,观察各组患者心房快速刺激前后心房有效不应期 (AERP)、AERP频率自适应性、不应期离散度 (AERPd)的变化及房颤诱发情况。结果　①心房快速起搏后 ,对照组AERP明显缩短 ,依那普利组AERP无显著变化。两组患者心房快速起搏前后AERPd差异无显著性 ;②心房快速起搏前后 ,对照组右心耳 (RAA)处AERP与相应程控刺激基础周长拟合直线的斜率分别为 0 0 6 2和 0 0 18;依那普利组分别为 0 0 5 9和 0 0 5 3;③心房快速起搏后 ,对照组房颤诱发例数、次数显著增加 ,平均房颤持续时间明显延长 ;依那普利组心房快速起搏前后房颤诱发情况无显著差异。结论　依那普利能够防止心房快速激动引起的心房急性电重构 ,降低房颤诱发率     

Age-related changes in the atrial muscarinic type 2 receptor and their effects on atrial fibrillation vulnerability in rabbits

Aging plays an important role in increased vulnerability to atrial fibrillation (AF). Mediated by activity at the muscarinic type 2 receptor (M2R), the parasympathetic nerve contributes to the onset of AF. The purpose of this study was to investigate whether aging changes the distribution of M2R in the atrial myocardium and to determine the impact of these changes on AF vulnerability. Expression of M2R in the atrial myocardium was evaluated by immunostaining and Western blot in three groups—young (3 months old), mature (8 months old) and senescent (36–48 months old) rabbits. AF inducibility was recorded with and without cervical vagal stimulation (VS) in vivo in all groups. AF inducibility, the atrial effective refractory period (AERP) and the monophasic action potential (MAP) were recorded in an additional seven senescent rabbits before and after topical administration of tropicamide. The results showed that the density of M2R in the left atrial free wall (LAFW) was significantly higher than that in other parts of the atria. The left atrial appendage had a higher level of M2R expression than the right atrium. The M2R density of the epicardial side was greater than that of endocardial side in both atria. The senescent group had a significant increase in M2R expression in the LAFW relative to the mature group. AF inducibility was also higher in the senescent group than in the other two groups. After tropicamide administration in the senescent rabbits, AF inducibility decreased significantly, the VS-induced decrease in AERP and MAP duration at 90% repolarization (MAPD90) of LAFW was attenuated, and the dispersion of the AERP and MAPD90 increase was attenuated. In conclusion, our results suggested that there is spatial heterogeneity in the M2R distribution in the atria of the rabbit. The density of M2R in the LAFW increased with the aging of rabbits. This change in M2R enhanced the heterogeneity of the M2R distribution and contributed to the change in age-related AF vulnerability.     

Intermittent interatrial block after electrical cardioversion for atrial fibrillation

A 67-year-old woman with persistent atrial fibrillation presented for elective electrical cardioversion. The patient was cardioverted to normal sinus rhythm with a synchronized 150 joules (J) biphasic shock. Varying P-wave morphology suggesting intermittent interatrial block (IAB) was noted after the cardioversion on the rhythm strip. Three minutes later the patient developed early recurrence of atrial fibrillation and a second successful 150 J biphasic shock was delivered; IAB was still evident on a single lead II monitoring. However, the patient remained in sinus rhythm. The patient was discharged in normal sinus rhythm with electrocardiographic evidence of intermittent interatrial block. This case report examines the occurrence of IAB postcardioversion for atrial fibrillation and speculates on its prognostic significance.