曲美他嗪对家兔快速心房起搏心房电重构及心房肌细胞超微结构的影响

发布时间：2018-04-02 22:21

  本文选题：心房颤动　切入点：心房快速起搏　出处：《河北医科大学》2014年硕士论文

【摘要】：目的：心房颤动（Atrial Fibrillation）简称房颤（AF）,是临床最常见的心律失常之一，也是老年人心脏衰竭和血栓形成的常见危险因素。由于房颤的发病机制复杂，截至目前尚未完全阐明。以往研究认为心房电重构与房颤的发生紧密相关，近来研究发现房颤患者心肌超微结构在房颤发作期间发生了变化，即患者心房肌发生了结构重构。本研究使用人工心脏起搏的方法制备家兔急性房颤的动物模型，观察改善心肌能量代谢药物曲美他嗪对心房电重构及结构重构的干预影响，从而探讨房颤防治的新途径。 方法：由河北医科大学动物实验中心提供普通成年家兔20只，雌雄不拘。分别测量其心率(HR)、体重（BM）后，随机分为2组(每组10只)：生理盐水组（对照组），曲美他嗪组（实验组）。曲美他嗪组以曲美他嗪8mg/(kg.d)灌胃给药3周。生理盐水组以等容量的生理盐水灌胃3周。家兔麻醉后颈部正中切口，予气管插管、分离颈内静脉，穿刺置入1根4F双极电极导管至右心房，用BL-420生物机能实验系统(成都泰盟科技有限公司生产)同步记录体表心电图和右房心电图，当右房心电图显示小V波、大A波时，固定电极导管，分别测量两组家兔刺激周长为200ms和150ms时的心房有效不应期，然后分别以600次/min的频率行快速心房起搏，测定起搏8h后及起搏停止30分钟后的心房有效不应期。并于处死动物后1分钟内开胸，于无菌状态下取右心耳部心肌组织，制备电镜观察标本，应用透射电镜观察其超微结构。 将实验数据应用SPSS13.0统计软件进行统计学分析，采用均数±标准差表示符合正态分布的计量资料，采用重复测量设计方差分析进行组间比较，采用单因素方差分析进行组内比较。检验水准为α=0.05。 结果： 1心房电生理重构进程 生理盐水组，AERP200和AERP150在基础状态测量值分别为112.61±9.0ms和103.55±4.8ms。经快速起搏8小时后分别为97.30±6.8ms和93.24±5.0ms，与基础状态时比较具有统计学差异（P0.05）(表1)。经快速起搏8小时后与基础状态时AERP200和AERP150比较，分别缩短15.32±3.5%(P0.01)和10.31±1.5%(P0.01)。两者比较AERP200缩短值较AERP150缩短值更为显著（P0.05），说明发生了ERP的频率自适应性的下降。 2曲美他嗪对心房电重构的影响 曲美他嗪组起搏前后AERP无明显缩短，AERP200和AERP150在基础状态下分别为113.91±9.6ms和103.33±4.7ms，经过8小时快速起搏后分别为115.44±8.0ms和103.33±4.5ms，起搏前后比较无统计学差异（P0.05）(Table1)。 3停止起搏30分钟后对电重构的影响 对照组AERP200和AERP150在停止快速起搏30分钟后分别为111.33±8.7ms和102.44±5.5ms，曲美他嗪组AERP200和AERP150在停止快速起搏30分钟后分别为115.93±8.3ms和102.41±4.4ms，均较基础水平无显著变化（P0.05）(Table1)。 4心房肌细胞超微结构变化 生理盐水组经过8小时快速心房起搏后心房肌细胞可见肌纤维连续性受损，肌原纤维消失，核周高度水肿，线粒体肿胀、变形、部分溶解、消失，，粗面内质网高度扩张，可见散在脂滴及散在糖原颗粒（Fig.1，Fig.2，Fig.3，Fig.4）。 曲美他嗪组经过8小时快速心房起搏后心房肌细胞可见肌纤维有较好的连续性，肌原纤维轻度水肿，部分核周轻度水肿，线粒体水肿较轻、未见脂滴及糖原颗粒。明显减轻了快速起搏所导致的心房肌超微结构的改变（Fig.7，Fig.8，Fig.9，Fig.10，Fig.11，Fig.12）。 结论： 1快速心房起搏时可导致心房肌电重构且停止起搏后心房肌电重构可较快恢复。 2曲美他嗪可以预防和逆转快速心房起搏所导致的心房肌电重构。 3曲美他嗪可以减轻快速心房起搏所造成的心房肌细胞超微结构的改变。
[Abstract]:Objective: atrial fibrillation (Atrial Fibrillation) AF (AF), is one of the most common clinical arrhythmia, but also the common risk factors of elderly heart failure and thrombosis. Because the pathogenesis of atrial fibrillation complicated, so far has not been fully elucidated. Previous studies that are closely related to occurrence of atrial electrical remodeling and atrial fibrillation recently, the study found that patients with atrial fibrillation myocardial ultrastructure changes during atrial fibrillation, which occurred in patients with atrial structural remodeling. Animal models were prepared in rabbits with acute atrial fibrillation in this study using artificial cardiac pacing, observe the improvement of energy metabolism of drug intervention effect of trimetazidine on myocardial QuMei atrial electrical remodeling and structure the reconstruction, so as to explore new ways of treatment of atrial fibrillation.
Methods: from the experimental animal center of Hebei Medical University ordinary 20 adult rabbits of both sexes were measured. The heart rate (HR), weight (BM), were randomly divided into 2 groups (n = 10): normal saline group (control group), Sibutramine trimetazidine group (experimental group) QuMei trimetazidine group. Sibutramine trimetazidine 8mg/ (kg.d) by gavage for 3 weeks. The saline saline group by gavage for 3 weeks. The capacity of rabbits after anesthesia neck incision, tracheal intubation, separation of internal jugular vein puncture in 1 4F bipolar electrode catheter into the right atrium, the experiment system of BL-420 biological function (Chengdu taimeng Technology Co., Ltd. production) and right atrial electrocardiogram ECG, when right atrial ECG showed small V wave, A wave, fixed electrode catheter, two groups of rabbits were measured for 200ms and 150ms stimulate the perimeter of the atrial effective refractory period, and then to frequency 600 times fast /min Atrial atrial pacing was used to determine atrial effective refractory period after 30 minutes after pacing 8h and after stopping for 1 minutes. The right heart ear myocardium tissue was obtained under sterile condition, and electron microscopy was used to observe the specimen. The ultrastructure was observed by transmission electron microscope.
The experimental data were analyzed by statistics software SPSS13.0, expressed by the mean and standard deviation with normal distribution measurement data, using repeated measurement analysis of variance were compared between two groups using ANOVA to compare the group. The test level of alpha = 0.05.
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