A model for left juxtaposition of the atrial appendages in the chick

Abstract

The morphogenesis of most types of human congenital cardiac malformations is still obscure. The reasons for this are, first, the paucity of data from human embryos and fetuses and, second, the paucity of appropriate animal models. During the past few years, we have tested several chemicals for their teratogenic potential, hoping to find, particularly in the chick, substances that could be used for the development of models for specific cardiac malformations. We have now discovered that suramin, an antitrypanosomal drug, can induce a special type of congenital cardiac defect in which the two atrial appendages are positioned to the left of the great arteries. This situation resembles the situation found in humans and classified as left juxtaposition of the atrial appendages. In the present study, we have analysed the pathomorphological features of a series of our chicken hearts to assess precisely how accurately these cardiac malformations in the chick correspond to the situation seen in the human. We found that the cases observed in the chick did, indeed, have many features in common with the human cases described in the literature. This suggests that we have developed an animal model for human left juxtaposition. Our model could be used for two kinds of embryological studies: first, documentation of the morphogenesis of left juxtaposition; and second, studies on the mechanisms driving the normal positional changes between the atriums and outflow tract of the embryonic heart during the late phase of cardiac looping. The fact that left juxtaposition of the atrial appendages can be induced by suramin might help to elucidate the molecular mechanisms underlying this type of congenital cardiac malformation. Furthermore, the fact that suramin is used for the chemotherapy of frequent tropical diseases, such as African trypanosomiasis and onchocerciasis, poses the question as to whether this drug might play a role in the aetiology of left juxtaposition in some human populations.