PO-0501 Glibenclamide Closes Neonatal Ductus Arteriosus In Rats

Abstract

Background Treatment for patent ductus arteriosus (PDA) in premature infants may fail following perinatal indomethacin exposure. Glibenclamide, a sulfonylurea, constricts the fetal rabbit ductus in vitro , and fetal rat ductus in vivo . Clinical doses for diabetes include 0.1 mg/kg (adults) and 1 mg/kg (children with neonatal diabetes). Aims To show ductus constriction acceleration with Glibenclamide in newborn rats as a model of treatment for premature PDA. Methods Glibenclamide (1 mg/Kg) was injected intraperitoneally (IP) to newborn Wistar rats immediately after cesarian section, and the ductus diameter was studied at 60 min with rapid whole-body freezing, by cutting on a freezing microtome, and measurements performed on a microscope using a micrometre. Two near-term rat models were studied on the 21st day. In a chronic fetal indomethacin-exposure model, mother rats were treated with indomethacin (10 mg/kg, gavage) for two days before birth. In a hypoxia model, neonates were incubated in 8% oxygen. In a premature model, rats were delivered on the 19th day (two days before term) and incubated in 80% oxygen. Results In these three models, neonatal ductus constricted slowly. Glibenclamide 1 mg/kg, caused accelerated constriction and the effects were dose-dependent. Glibenclamide (1mg/kg, IP) was associated with hypoglycemia, which was controlled with 50% glucose via gavage. Conclusions Glibenclamide (1 mg/kg, IP) constricts the neonatal ductus in 60 min in three rat models. Hypoglycemia was controlled with glucose, indicating its usefulness in the treatment of PDA in premature infants.