Tetralogy of Fallot, truncus arteriosus, abnormal myocardial architecture and anomalies of the aortic arch system induced by bis-diamine in rat fetuses.

OBJECTIVES: The aim of this study was to analyze the relation between anomalies of the heart and aortic arch arteries in near-term rat fetuses exposed to the chemical bis-diamine.

BACKGROUND: Bis-diamine is known to induce cardiovascular anomalies.

METHODS: Bis-diamine was given orally to normal pregnant rats, and the 65 fetuses were examined under a dissecting microscope after formalin fixation.

RESULTS: There were 26 rat fetuses (40%) with a ventricular septal defect in the perimembranous portion, of which 14 (22%) had tetralogy of Fallot, 4 (6%) had truncus arteriosus and 8 (12%) had a relatively small defect with no other major anomalies. In 44 fetuses (68%) the middle latitudinal muscle bundle of the ventricular septum was continuous with the right ventricular free wall. There were, isolated or in association, a double- or right aortic arch in 6 fetuses (9%), aberrant subclavian arteries in 9 (14%), right ductus arteriosus in 12 (18%) and agenetic ductus in 4 (6%). The cross-sectional area of the ductus, as corrected by that of the aortic isthmus, was abnormally small in 47 rats (72%). The rat fetuses with a septal defect or abnormal myocardial architecture, or both, usually had a small ductus; it was very small or absent in those fetuses with tetralogy of Fallot. Of the four fetuses with truncus arteriosus, two had a vestigial vasculature on the truncus root and three had a rudimentary infundibulum.

CONCLUSIONS: The cardinal defect may be the anomalous and reduced development of the sixth arch arteries, which by imposing pressure overload on the fetal right ventricle, may have led to either or both the persistence of ventricular septal defect as a vent or the formation of myocardial architecture favorable for the generation of pressure in the right ventricle.