Common arterial trunk and pulmonary atresia: close developmental cousins? results from a teratogen induced animal model.

OBJECTIVES

To examine morphological similarities between "classically different" congenital heart lesion types induced in fetal rats by the cardiac teratogen N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine (bis-diamine).

METHODS

A single 200 mg oral dose of bis-diamine was given to 50 pregnant rats on the 9th gestational day. Eleven controls were fed an inert vehicle. Experimental and control rats were sacrificed from 15.4 days to term and embryos delivered by caesarean section. Age-matched embryos were processed for histology and sectioned at 7 microns. Cardiac morphology was compared between normal and bis-diamine exposed groups.

RESULTS

Hearts from control embryos were morphologically normal. Those from bis-diamine treated embryos exhibited common arterial trunk (32%), overriding aortic valve with valvar pulmonary stenosis (40%) or infundibular atresia (4%), or ventricular septal defect (24%). Development of the outlet septum was affected in all hearts and the arterial duct was absent in 72% of cases. Whilst most hearts demonstrated the anatomy expected for their lesion, some with a common arterial valve demonstrated a pulmonary blood supply similar to that in human cases of pulmonary atresia, where, in the absence of an arterial duct, an essential systemic to pulmonary conduit was provided by a "persistent fifth aortic arch artery". In one such case the proximal part of the aortopulmonary septum was identified above a common valve. The septum was deviated to the left and was not continuous throughout the length of the arterial trunk, causing atresia of the pulmonary component. Others had muscular infundibular atresia but with a pulmonary blood supply arising directly from the solitary trunk as seen in common arterial trunk "type III".

CONCLUSIONS

Bis-diamine consistently affects development of those structures which partition the arterial segment of the developing heart at one or more levels, often coexistent with agenesis of the sixth aortic arch arteries. Whilst the aortopulmonary and outlet septums were absent in most cases of common arterial trunk, some morphological duality was shared by classically different lesion types in these rat hearts, which may suggest a common aetiology for common arterial trunk "type III" and aortic overriding with absence of the outlet septum and pulmonary atresia.