曲美他嗪對家兔快速心房起搏心房電重構及心房肌細胞超微結構的影響
發(fā)布時間:2018-04-02 22:21
本文選題:心房顫動 切入點:心房快速起搏 出處:《河北醫(yī)科大學》2014年碩士論文
【摘要】:目的:心房顫動(Atrial Fibrillation)簡稱房顫(AF),是臨床最常見的心律失常之一,也是老年人心臟衰竭和血栓形成的常見危險因素。由于房顫的發(fā)病機制復雜,截至目前尚未完全闡明。以往研究認為心房電重構與房顫的發(fā)生緊密相關,近來研究發(fā)現(xiàn)房顫患者心肌超微結構在房顫發(fā)作期間發(fā)生了變化,即患者心房肌發(fā)生了結構重構。本研究使用人工心臟起搏的方法制備家兔急性房顫的動物模型,觀察改善心肌能量代謝藥物曲美他嗪對心房電重構及結構重構的干預影響,從而探討房顫防治的新途徑。 方法:由河北醫(yī)科大學動物實驗中心提供普通成年家兔20只,雌雄不拘。分別測量其心率(HR)、體重(BM)后,隨機分為2組(每組10只):生理鹽水組(對照組),曲美他嗪組(實驗組)。曲美他嗪組以曲美他嗪8mg/(kg.d)灌胃給藥3周。生理鹽水組以等容量的生理鹽水灌胃3周。家兔麻醉后頸部正中切口,予氣管插管、分離頸內(nèi)靜脈,穿刺置入1根4F雙極電極導管至右心房,用BL-420生物機能實驗系統(tǒng)(成都泰盟科技有限公司生產(chǎn))同步記錄體表心電圖和右房心電圖,當右房心電圖顯示小V波、大A波時,固定電極導管,分別測量兩組家兔刺激周長為200ms和150ms時的心房有效不應期,然后分別以600次/min的頻率行快速心房起搏,測定起搏8h后及起搏停止30分鐘后的心房有效不應期。并于處死動物后1分鐘內(nèi)開胸,于無菌狀態(tài)下取右心耳部心肌組織,制備電鏡觀察標本,應用透射電鏡觀察其超微結構。 將實驗數(shù)據(jù)應用SPSS13.0統(tǒng)計軟件進行統(tǒng)計學分析,采用均數(shù)±標準差表示符合正態(tài)分布的計量資料,采用重復測量設計方差分析進行組間比較,采用單因素方差分析進行組內(nèi)比較。檢驗水準為α=0.05。 結果: 1心房電生理重構進程 生理鹽水組,AERP200和AERP150在基礎狀態(tài)測量值分別為112.61±9.0ms和103.55±4.8ms。經(jīng)快速起搏8小時后分別為97.30±6.8ms和93.24±5.0ms,與基礎狀態(tài)時比較具有統(tǒng)計學差異(P0.05)(表1)。經(jīng)快速起搏8小時后與基礎狀態(tài)時AERP200和AERP150比較,分別縮短15.32±3.5%(P0.01)和10.31±1.5%(P0.01)。兩者比較AERP200縮短值較AERP150縮短值更為顯著(P0.05),說明發(fā)生了ERP的頻率自適應性的下降。 2曲美他嗪對心房電重構的影響 曲美他嗪組起搏前后AERP無明顯縮短,AERP200和AERP150在基礎狀態(tài)下分別為113.91±9.6ms和103.33±4.7ms,經(jīng)過8小時快速起搏后分別為115.44±8.0ms和103.33±4.5ms,起搏前后比較無統(tǒng)計學差異(P0.05)(Table1)。 3停止起搏30分鐘后對電重構的影響 對照組AERP200和AERP150在停止快速起搏30分鐘后分別為111.33±8.7ms和102.44±5.5ms,曲美他嗪組AERP200和AERP150在停止快速起搏30分鐘后分別為115.93±8.3ms和102.41±4.4ms,均較基礎水平無顯著變化(P0.05)(Table1)。 4心房肌細胞超微結構變化 生理鹽水組經(jīng)過8小時快速心房起搏后心房肌細胞可見肌纖維連續(xù)性受損,肌原纖維消失,核周高度水腫,線粒體腫脹、變形、部分溶解、消失,,粗面內(nèi)質(zhì)網(wǎng)高度擴張,可見散在脂滴及散在糖原顆粒(Fig.1,F(xiàn)ig.2,F(xiàn)ig.3,F(xiàn)ig.4)。 曲美他嗪組經(jīng)過8小時快速心房起搏后心房肌細胞可見肌纖維有較好的連續(xù)性,肌原纖維輕度水腫,部分核周輕度水腫,線粒體水腫較輕、未見脂滴及糖原顆粒。明顯減輕了快速起搏所導致的心房肌超微結構的改變(Fig.7,F(xiàn)ig.8,F(xiàn)ig.9,F(xiàn)ig.10,F(xiàn)ig.11,F(xiàn)ig.12)。 結論: 1快速心房起搏時可導致心房肌電重構且停止起搏后心房肌電重構可較快恢復。 2曲美他嗪可以預防和逆轉(zhuǎn)快速心房起搏所導致的心房肌電重構。 3曲美他嗪可以減輕快速心房起搏所造成的心房肌細胞超微結構的改變。
[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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