日本小児循環器学会雑誌 Pediatric Cardiology and Cardiac Surgery

Bis-diamine, a potent teratogen, induces conotruncal diseases and thymic hypoplasia in rats similar to chromosome 22q11 deletion syndrome in humans. The precise mechanism underlying cardiac teratogenic effects of bis-diamine remains unknown. On the 10th day of gestation, 200 mg bis-diamine was administered to 40 pregnant rats. The fetuses were delivered by Cesarean section after the cervical dislocation of rats on the 21st day of gestation and were immediately frozen in acetone cooled to −76°C using dry ice. Each frozen thorax of the fetus was transversely cut, and the section surface was serially photographed with a stereoscopic microscope (Wild M400 Photomacroscope) at every 500 µm. The following cardiac diseases were recorded in 330 fetuses: Tetralogy of Fallot (16％), Tetralogy of Fallot with absent pulmonary valve (14％), Tetralogy of Fallot with pulmonary valvular and infundibular atresia (38％), truncus arteriosus (10％), ventricular septal defects (3％), interrupted aortic arch type B (2％), and atrioventricular septal defects (2％). Fetuses with the Tetralogy of Fallot and absent pulmonary valve showed pulmonary arteries aneurysmally dilated at the right and left pulmonary hila, obstructing the adjacent bronchus. Fetuses with atrioventricular canal defects showed thick nodular atrioventricular valve leaflets and signs of congestive heart failure, including the enlargement of all cardiac chambers and increased pericardial effusion. In addition, vascular diseases (right aortic arch, aberrant subclavian artery, and vascular ring) complicated the cardiac diseases. Thymus hypoplasia occurred in all fetuses (100％), while some fetuses developed diaphragmatic hernia (10％). No aortopulmonary collateral artery was noticed. These cross-sectional morphologies represent fetal echocardiographic diagnoses indicating congenital heart diseases associated with chromosome 22q11.2 deletion syndrome in rat model.