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

In-situ cross-sectional morphology of the fetal and neonatal rat ductus arteriosus (DA) is studied by rapid whole-body freezing, cutting on a freezing microtome, and photographing the cross-section serially every 0.5 mm with a stereoscopic microscope (Wild M400). Thoracic sagittal sections reveal the right ventricular (RV) infundibulum, main pulmonary artery, DA, and descending aorta in one plane. This forms the major circulatory route in the fetus. Serial frontal and sagittal sections of the neonatal thorax reveal rapid tubular constriction at 1 hour and complete closure at 2 hours after birth. Fetal DA shows different patterns of pharmacological constriction. Fetal DA constriction by indomethacin is initially tubular at 1 and 2 hours after orogastric administration to the mother rat but becomes sandglass shaped and eventually becomes distal, short, tubular, or membranous at 8 and 24 hours after administration. These patterns of constriction are observed after pharmacological agents are administered transplacentally or directly to the fetus; this includes DA constriction after administration of cyclooxygenase inhibitors such as aspirin, indomethacin, and ibuprofen, constriction after administration of glucocorticoid hormones such as betamethasone, and constriction after administration of sulfonylureas such as glibenclamide and glimepiride. Persistent fetal DA constriction after administration of indomethacin for more than 24 hours induces RV concentric hypertrophy with diminished cavity and left ventricular dilatation with increased ventricular muscle mass in 4-chamber view sections.