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背景:应用左向右分流大鼠模型可以研究慢性肺血管重构在成人型先天性心脏病中的发病机制。目的:观察慢性左向右分流大鼠模型慢性肺动脉高压形成的特点。设计、时间及地点:随机对照动物实验,于2008-04/2009-04在解放军第三军医大学新桥医院动物实验中心完成。材料:4周龄SPF级纯系健康SD大鼠80只,体质量95～110g。随机分为对照组、分流组,每组40只。自制改良聚乙烯血管连接套管,近心端内外径分别为0.6mm和0.8mm,远心端内外径分别为0.8mm和1.0mm,长1.6mm。方法:分流组大鼠:行左向右分流术,运用收缩型聚乙烯血管连接器建立右颈总动脉-颈外静脉连接。对照组行假手术。手术后在第4,8,12,16周(每个时相点10只大鼠),通过血流动力学检查、病理标本制作、苏木精-伊红染色、图像分析等一系列步骤对该模型进行评价。主要观察指标:分流组和对照组大鼠右室收缩压、右心肥大比率[右室(/左室+室间隔)],各级肺小动脉相对中膜厚度改变。结果:全部实验动物存活。分流组肺循环血流量明显高于对照组(P<0.01)。与对照组相比,分流12,16周右室收缩压明显增高(P<0.01),分流12,16周时右心肥大比率显著增加(P<0.01)。与对照组相比,分流12周和16周组肺动脉相对中膜厚度明显增加(P<0.01)。结论:左向右的持续低分流,能有效引起慢性肺血管重构,颈总动脉-颈外静脉连接建立慢性肺动脉高压模型操作简便,稳定性好,对实验动物损伤小,是研究低分流引起的慢性肺动脉高压形成的有用工具。
BACKGROUND: The left-to-right shunt rat model can be used to study the pathogenesis of chronic pulmonary vascular remodeling in adult congenital heart disease. Objective: To observe the characteristics of chronic pulmonary hypertension in chronic left-to-right shunt rat model. DESIGN, TIME AND SETTING: The randomized controlled animal experiment was performed at the Animal Experimental Center, Xinqiao Hospital, Third Military Medical University, People’s Liberation Army from April 2008 to April 2009. MATERIALS: Eighty SPF pure healthy SD rats aged 4 weeks were enrolled. The body weight was 95 ~ 110g. Randomly divided into control group, shunt group, 40 rats in each group. Homemade modified polyethylene vascular access cannula, the proximal and distal diameter were 0.6mm and 0.8mm, distal end of the inner diameter of 0.8mm and 1.0mm, length 1.6mm. Methods: The shunt group rats: left to right shunt, the use of shrinkage polyethylene vascular connector to establish the right common carotid artery - jugular vein connection. Control group sham operation. After the operation, we took a series of steps such as hemodynamic examination, pathological specimen preparation, hematoxylin-eosin staining and image analysis on the 4th, 8th, 12th and 16th weeks (10 rats at each time point) The model is evaluated. MAIN OUTCOME MEASURES: Right ventricular systolic pressure and ratio of right ventricular hypertrophy [right ventricular (/ LV + interventricular septum)] in shunt group and control group were observed. Results: All experimental animals survived. The shunting group pulmonary blood flow was significantly higher than the control group (P <0.01). Compared with the control group, right ventricular systolic pressure was significantly increased at 12 and 16 weeks (P <0.01), right ventricular hypertrophy rate was significantly increased at 12 and 16 weeks (P <0.01). Compared with the control group, the relative media thickness of pulmonary artery was significantly increased at 12 and 16 weeks of shunting (P <0.01). CONCLUSIONS: Left-to-right continuous low shunt can effectively induce chronic pulmonary vascular remodeling. The establishment of chronic pulmonary hypertension model with common carotid artery-external jugular vein connection is simple and convenient, with good stability and less damage to experimental animals. A useful tool for the formation of chronic pulmonary hypertension.