Functional Characteristics in the Embryo of Mouse Model of Transposition of the Great Arteries

本实验采用全反式维甲酸（all-trans-retinoic acid，ATRA）对孕鼠进行处理，试图建立一种较好的小鼠大动脉转位（translocation of the great arteries，TGA）模型，并在孕8.5天给予ATRA 70 mg/kg，成功地建立了90%胚胎发生TGA的模型。利用该模型，我们发现近端流出道肿胀发育不良导致正常心室-动脉关系的失败，并导致心室与大动脉的平行连接，即右心室（RV）与主动脉（Ao）和左心室（LV）与肺动脉（PA）。我们认为，重要的是要找到它的形态发生的血液动力学的作用，并建立了技术，其中哺乳动物胚胎在显微镜下原位观察和心脏的活动，而它仍然活着和可行的高速摄像机记录。结果表明，TGA模型胚胎原始心室流出道存在两种血流模式：一种是RV至Ao的血流与LV至PA的血流平行分离;另一种是右室流出的血流同时进入主动脉和肺动脉，后者可能导致TGA合并排列不齐型室间隔缺损，或者在极端情况下是右心室双出口。分析TGA胚胎的心室大小和功能，发现TGA胚胎的RV比对照组小，射血分数低，提示血流动力学在TGA发病中可能起一定作用。

We had been trying to make a good model of transposition of the great arteries (TGA) in the mouse by treating pregnant dams by all-trans retinoic acid, and finally established the model in which TGA was induced in 90% of embryos by giving the drug with a dose of 70mg/kg at 8.5 days of gestation. Using this model, we have found that hypo-dysplasia of proximal outflow swelling causes failure of the normal ventriculo-arterial ralation and leads to parallel connection of the ventricles to the great arteries, i.e.the right ventricle (RV) to the aorta (Ao) and the left ventricle (LV) to the pulmonary artery (PA). We have then considered that it is important to find the role of hemodynamics in its morphogenesis, and established the technique in which the mammalian embryo is observed in situ under a microscope and action of the heart is recorded with a high speed video camera while it is still alive and viable. Using this method, it was found that there was two pattaerns of flow through outflow tract of the primitive ventricle in TGA model embryos ; one is that flow from RV to Ao was parallel to and separated from it from LV to PA ; the other was that flow from RV goes into both Ao and PA.The latter likely destined to TGA associated with malalign type ventricular septal defect, or double outlet right ventricle in an extreme case. Analysing the ventricular size and function, RV was smaller and lower in ejection fraction in TGA embryos than in controls, suggestings some possible role of hemodynamics in pathogenesis of TGA.