Experimental Study on Pathogenesis and Morphogenesis of Congenital Heart Defects : Conotruncal Abnormality Produced by Bis(dichloroacetyl)diamine

Abstract

Many problems as to the morphogenesis of cardiovascular malformations remain unsolved. The morphogenesis of a series of conotruncal anomalies presents particularly difficult problems. The authors administered bisdiamine to rats for the purpose of clarifying the morphogenesis of conotruncal anomalies, establishing their critical periods, and extrapolating these findings to the morphogenesis of cardiac malformations in man. We were able to induce numerous experimental cardiac malformations by singly administrating 200mg bisdiamine orally to rats on the 9th, 9.5th, 10th, and 11th day after conception. Among these cardiac malformations, 82.6% proved to be persistent truncus arteriosus and cardiac anomalies corresponding to tetralogy of Fallot in man, followed by 15.2% of aortic arch anomalies including vascular ring, right aortic arch, and aberrant subclavian artery. Extracardiac malformations observed included corneal extrusion, diaphragmatic hernia, cleft lip, and abnormal lobulation of the right lung. Thymus weight was significantly less than that of the control (P<0.001), with the gland showing in-sufficient lobulation and descent. Histologically, depletion of lymphocytes in the thymic cortex and loss of cortico-medullary demarcation was detected, being diagnosed as hypoplasia. The authors conclude from these findings that the malformation complex caused by administration of bisdiamine might be used as an experimental model of the DiGeorge syndrome. It is presumed that its critical period would correspond to the third to fourth week of gestation in man.