Transposition of the great vessels and other cardiovascular abnormalities in rat fetuses induced by trypan blue

Abstract

Complete and partid transposition of the great vessels, dextrocardia, and absence or stenosis of the tricuspid or mitral valves were encountered singly or in combination in rat fetuses from mothers injected with trypan blue solution subcutaneously on the 8th or 9th day of gestation. Hearts with transposition of the great vessels were usually characterized by shortness of the aorta and pulmonary trunk, cranial location of the aortic valve, displacement of the coronary arteries, and a channel or "track" extending from the cranial portion (infundibulum) of the right ventricle to the commencement of the transposed pulmonary trunk. Inadequate expansion of the atrioventricular ring about the 12th or 13th day of gestation possibly leads to deformity of the atrioventricular cushions and to absence or stenosis of the tricuspid or mitral valves. Sinuosity of the truncus arteriosus seen in many 13th day and older embryos of the trypan blue series is considered a significant factor in the development of transposition of the great vessels.

Teratogenic effects of suramin on the chick embryo

“…It has been proven to be teratogenic in mammalian as well as in avian embryos and it has been found to cause similar malformations in both classes of vertebrates. Among these abnormalities are developmental defects of the caudal trunk (Hamburgh 1954;Kaplan and Grabowski 1967;Lendon 1975;Iwai 1989), cardiovascular malformations, such as abnormal branching patterns of the aortic arch arteries and juxtaposition of the right atrial appendage Goss 1956, 1957;Adams Smith 1963;Stéphan and Mick 1963;Monie et al 1966), and median facial clefts (Beaudoin and Wilson 1958;Smith and Monie 1969). The similarity to the malformation spectrum found in the present study is striking.…”

“…Only two publications show such malformations, one in rats (Smith and Monie 1969) and one in chicks (Beaudoin and Wilson 1958). Juxtaposition of the right atrial appendage, which occurred in one-third of our suramin-treated chick embryos, occurred at a similar frequency following administration of trypan blue to mice and rats Goss 1956, 1957;Adams Smith 1963;Monie et al 1966). In chick embryos, however, trypan blue was found to produce defects of the ventricular septum (Jaffee 1965).…”

Cardiovascular malformations experimentally induced in the rat

“…In the vast category of malformations caused in rats by trypan blue. a high frequency of transpositions of the great vessels, associated with alterations of the cardiac valves and septa was noted [ Fox and Goss, 1958;Monie et al, 1966], X-ray irradiation of pregnant rats at 9 days of gestation causes a variety of malfor mations to the newborns, e.g. anomalies of the atrial, atrioventricular and ventricular septa and transposition of the great vessels Wilson et ai, 1953], Ventricular septum defects have been noticed in rat and mouse fetuses whose mothers had been exposed to hypoxia [Clemmer and Telford, 1966], hyperoxia [ Miller et ai, 1971] and to carbon dioxide [Haring,I960].…”

The role of embryology in teratological research, with particular reference to the development of the neural tube and heart

“…In experimental studies in which early rat embryos were treated with Trypan blue (Monie, Takacs & Warkany, 1966) or by ionizing irradiation (Fox & Goss, 1957) transposition of the great vessels was occasionally produced. In all cases, this condition was associated with abnormalities in looping of the primitive heart tube.…”