Fetal rabbit ductus arteriosus assessed in a teratological study on isoproterenol and metaproterenol

Abstract

Five groups, including an untreated control group, of mated New Zealand white female rabbits were used for a teratological study in which isoproterenol sulfate and metaproterenol sulfate were fed separately in the diet, each at 50 and 16 mg/kg/day expressed in terms of free base, on days 7–16 after mating. Twenty-eight-day-old fetuses were delivered by cesarean section, and survival during 6 hours in an incubator prior to sacrifice was determined. Of the 237 viable rabbit fetuses delivered, 201 survived the 6-hour incubation. Of these survivors, 93 had red-colored latex injected into the pulmonary arch and had heart and lungs preserved satisfactorily for examination to determine that the ductus arteriosus was open in 70 and barely open in 23. Injection of dyed latex into the aortic arch of eight similar fetuses, however, did not reveal the status of the ductus arteriosus. Suitable magnification near the junction of the fetal rabbit ductus arteriosus with the aorta, showed a pair of flaps which are valvelike and permit only unidirectional blood flow. Latex injected into the aortic arch thus could not enter the ductus arteriosus. No evidence of any teratogenic effect was found with either isoproterenol or metaproterenol.