No abstract

Administration of N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine, bisdiamine, in pregnant Donryu rats on day 10 of gestation induces a high incidence of cardiovascular anomalies in fetuses. Bisdiamine administration induced aplasia of the sixth aortic arch artery, with both the right and left primitive pulmonary arteries being directly linked to the truncus, and resulting in four types of malformation of pulmonary arteries (PAs). When two primitive PAs shared a single root, the consequence was either pulmonary trunk hypoplasia, as is seen in tetralogy of Fallot, or type I persistent truncus arteriosus (PTA) as classified by Collet and Edwards. When root portions of two PAs did not fuse, either type II or type III PTA resulted. In controls, the right dorsal aorta (DA) between the right seventh intersegmental artery (IA) and the site where both DAs fuse degenerated and the left aortic arch (AA) and the right subclavian artery (SA) were formed. Bisdiamine administration induced two additional types of vascular anomalies. In one of these, the right DA between the right 4AA and the right 7IA degenerated and a left AA accompanied by an aberrant right SA resulted. In the other type, the left DA between the left 4AA and the left 7IA degenerated and a right AA accompanied by an aberrant left SA resulted. These results indicate that administration of bisdiamine induces malformation in the great blood vessels by disturbing persistency and degeneration of aortic arch arteries and DAs.

Administration of N, N'‐bis (dichloroacetyl)‐l,8‐octamethylenediamine, bisdiamine, to pregnant Donryu rats on a single day of gestation induced unilateral and bilateral diaphragmatic hernias in fetuses with high incidence. The protruded liver was not covered with a serous membrane or a muscular layer. Incidence of unilateral diaphragmatic hernia on the left side was high when bisdiamine was administered on day 9 or 13 of gestation, and that on the right side was high when administered on day 12 of gestation. Incidence of bilateral diaphragmatic hernia was high when bisdiamine was administered on day 12 of gestation. Differences in sensitivity to hernia formation according to day of bisdiamine administration between right and left sides may reflect differences in developmental chronology between the two sides. Two distinct times for induction of left diaphragmatic hernia might be attributed to at least two different mechanisms. The present model is expected to help analyzing not only anatomical characteristics of congenital diaphragmatic hernia but also possible mechanisms responsible for their development.

A high incidence of atrioventricular septal defect was induced in rat fetuses by administration of N, N ‐his (dichloroacetyl)‐1, 8‐octamethylenediamine, bisdiamine, to pregnant Donryu rats. Induction of atrioventricular septal defect was highly dependent on day of bisdiamine administration. When bisdiamine was administered singly on day 9.4 of gestation or consecutively on days 9 and 10 of gestation, the incidence of atrioventricular septal defect in fetuses increased. Survival rate decreased with increase in the amount of bisdiamine administered. Normalized incidence 5 for atrioventricular septal defect, which was calculated as a product of incidence and survival rate, was as high as 54.5% when 175 mg bisdiamine was administered on day 9.4 of gestation. Atrioventricular septal defect thus formed was of the complete type associated with either persistent truncus arteriosus or tetralogy of Fallot, indicating that the conotruncal portion was unexceptionally malformed. The present model is useful for analysis of development and pathogenesis of atrioventricular septal defect and also contributes to clarifying the normal development of atrioventricular valves and septa.