Increased Ductal Responsiveness to PGE2 after Maternal Treatment with Aspirin and Ibuprofen.

Abstract

ABSTRACT. This work was conducted to determine whether aspirin and ibuprofen, when administered prenatally may potentiate a reopening of the neonatal ductus arteriosus (DA) induced by PGE 2 after postnatal closure. In the first experiment, a subcutaneous injection of PGE 2 (4 µg) was administered to newborn rats 3 hr after a Cesarean delivery from pregnant females which had been orally given 100 or 300 mg/kg/day of aspirin and 10 or 30 mg/kg/day of ibuprofen on days 18, 19 and 20 of gestation. The ratio of the DA to the pulmonary artery (PA) was determined at intervals after the injection. The DA/PA ratio was significantly higher in newborn rats from mothers who were transplacentally administered these agents than the control. We also examined the hypothesis that maternal treatment with nonsteroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen, inhibits the catabolism of PGE 2 and that the increased reopening of the DA was partly due to this inhibition. 15-hydroxy prostaglandin dehydrogenase (15-PGDH) in neonatal lungs, the key enzyme involved in catalyzing PGE 2 to convert it to its inactive metabolite 15-keto-PGE 2 , was not affected by maternal treatment with aspirin and ibuprofen. These results suggest that the increased ductal responsiveness to PGE 2 in newborn rats was a common response after maternal NSAID treatment, but the catabolism of PGE 2 in the lungs did not always contribute to this response. -KEY WORDS: neonatal lung, PGE 2 catabolism, re-opening.J. Vet. Med. Sci. 60(3): 377-379, 1998 females were caged individually thereafter.In the first experiment, the effect of prenatal aspirin and ibuprofen treatment on the re-opening of the DA induced by PGE 2 was examined. Aspirin (100, 300 mg/kg/day) and ibuprofen (10, 30 mg/kg/day) administration was carried out on days 18, 19 and 20 of gestation. Pregnant females given only saline served as the controls. Females were killed by decapitation at 1 p.m. on day 21 of gestation at least 24 hr after the last drug administration, and the newborn pups were immediately obtained by Cesarean delivery. Only male pups were used in this study. The pups were placed in a humid chamber at 37°C and maintained for 3 hr after the Cesarean delivery, at which time the DA would have been completely closed under normal conditions [5]. Then, each pup was given a subcutaneous injection of 4 µg of PGE 2 (Sigma Chemical Co., St. Louis) dissolved in 50 µl of physiological saline. The pups were returned to the same chamber until their DAs and pulmonary arteries (PAs) were measured. The calibrations were made 0, 15, 30, 60, 90 and 180 min after the injection.Each pup was rapidly frozen in an acetone-dry ice mixture at the time of death. The frozen pups were weighed and then 4 or 5 pups of similar weight were selected from each litter and stored for a couple of days at 20°C until the DA and PA were measured. Measurements were obtained by the whole-body freezing and shaving method described elsewhere [2], and the DA/PA ratio was obtained by previously described meth...

Premature closure of ductus arteriosus after a single dose of diclofenac during pregnancy

“…The association between NSAIDs and DA closure is further supported by several experimental pharmacokinetics and pharmacodynamics studies using animal models. In these studies, different routes of administration (systemic, topical), and different NSAIDs (naproxen, aspirin, ibuprofen, diclofenac) caused fetal duct constriction 48 49. Finally, the association between NSAIDs and premature closure of patent ductus is also supported by the accumulating evidence on its use in the treatment of patent DA in neonates 17 50.…”

Habituelle Abortneigung

“…-Anti-Cardiolipin (IgM, IgG) mittlere bis hohe Titer -Anti-ß2-Glykoprotein I -(IgM, IgG) hohe Titer -Lupus-antikoagulanz CME te eine ASS-100-Gabe nur bis zu 32 + 0 SSW erfolgen [23,59]. Darüber hinaus kann Acetylsalicylsäure das Einsetzen der Wehen verzögern und aufgrund der thrombozytenaggregationshemmenden Wirkung sowohl mütterliche als auch fetale Komplikationen hervorrufen [55].…”