Effects of antenatal glucocorticoid administration on ductus arteriosus of preterm lambs.
We have previously shown that the incidence of patent ductus arteriosus (PDA) in premature infants whose mothers received prenatal glucocorticoid therapy was significantly lower than that of an untreated group. In addition, the incidence of respiratory distress syndrome was lower in the treated than in the untreated group. To determine whether glucocorticoids affect the ductus arteriosus itself, we studied the effects of a 48-h intravenous infusion of 1 mg/h hydrocortisone in prematurely born lambs (120-129 days, 0.84 gestation). Estimations of ductus patency were made on 1-h-old lambs by radioactive microsphere injections. We found that hydrocortisone infusions facilitate the closure of the ductus without altering the severity of respiratory distress in premature lambs. In the lamb, prostaglandin E2 (PGE2) inhibits the ability of the ductus to contract in response to O2. Because production of PGE2 has been shown to be inhibited by hydrocortisone in several isolated organ systems, we measured PGE2 plasma concentrations in treated and untreated animals. We found circulating PGE2 concentrations to be similar in the two groups; furthermore, release of PGE2 by isolated ductal rings in vitro was similar in treated and untreated animals. This contradicts the hypothesis that diminished PGE2 concentrations, either circulating or in the tissue, are the cause for ductus arteriosus closure in hydrocortisone-treated animals. However, hydrocortisone treatment decreases the sensitivity of the ductus arteriosus in vitro to the relaxing action of PGE2. These findings suggest that glucocorticoid treatment decreases the incidence of PDA in premature infants by affecting the interaction of PGE2 with ductal tissue.
D000818:Animals; D015232:Dinoprostone; D004373:Ductus Arteriosus / Q000187:drug effects / Q000196:embryology*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000097:blood; D006854:Hydrocortisone / Q000494:pharmacology*; D011247:Pregnancy; D011458:Prostaglandins E / Q000097:blood / Q000378:metabolism; D012756:Sheep
D005938:Glucocorticoids; D011458:Prostaglandins E; D015232:Dinoprostone; D006854:Hydrocortisone