Anomalies of the aortic arch and arterial duct induced by small doses of bis-diamine in fetal rats

Abstract

AbstractDeletion of chromosome 22 and DiGeorge syndrome are associated with inappropriate development of the neural crest and abnormalities of the ventricular outflow tracts. Bis-diamine induces comparable cardiac anomalies by inhibiting the normal development of the neural crest. In order to clarify the effect of damage on the development of the neural crest and its relation to the cardiac anomalies, the effects of giving a small dose of bis-diamine were compared with the results of a large dose of bis-diamine. A small dose of bis-diamine (20 mg), therefore, was administered to 40 pregnant rats on the 10th day of pregnancy, and 330 fetal hearts were studied on the 21st day with the rapid whole-body freezing method. Intracardiac anomalies were rare, being found in only 55 fetuses. The anomalies discovered were: aberrant origin of the subclavian artery in 88 fetuses, right aortic arch in 26 fetuses, interruption of the aortic arch in 23 fetuses, and high location of the aortic arch in 8 fetuses. Anomalies of the arterial duct were also common; with a vascular ring formed by the aortic arch and contra-lateral duct being seen in 21 fetuses, isolation of the right subclavian artery associated with either bilateral ducts (9 fetuses) or a right duct and absent left duct (9 fetuses), absent duct with tetralogy of Fallot in 7 fetuses, and with common arterial trunk in one fetus. In conclusion, a small dose of bis-diamine induced extra cardiac anomalies of the aortic arch and arterial duct, indicating a greater susceptibility of the aortic arch and the duct to inappropriate formation of the neural crest cells in the early developing embryo. Clinically, these anomalies of the aortic arch and the duct should be searched for in all patients suspected of having deletion of their 22nd chromosome.