Effects of antenatal glucocorticoid administration on ductus arteriosus of preterm lambs

Abstract

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.

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

“…Many of these markers of prematurity are improved by exogenous glucocorticoid treatment. Glucocorticoids facilitate the closure of the ductus arteriosus by inhibition of prostaglandin E 2 efficacy (Clyman et al 1981, Eronen et al 1993. They are also an effective treatment for refractory systemic hypotension in preterm infants, either alone or in combination with other volume expansion/ionotropic agents (Noori et al 2006, Ibrahim et al 2011.…”

The Effects of Caffeine on the Preterm Sheep Ductus Arteriosus

“…(1-10), in vivo studies suggest that postnatal constriction is primarily determined by a shift in the balance between oxygen (a ductus constrictor) and prostaglandins and nitric oxide (ductus dilators) (11,12). Alterations in antenatal glucocorticoid concentrations and postnatal pulmonary vascular resistance also play roles in in vivo ductus constriction (13,14).Recently, a randomized, placebo-controlled, multicenter trial was performed to evaluate the effects of caffeine administration in preterm infants (15). Infants were enrolled in the trial during the first 10 d after birth, and the primary goal of the study was to evaluate the long-term effects of caffeine on neurodevelopmental outcome.…”

“…(1-10), in vivo studies suggest that postnatal constriction is primarily determined by a shift in the balance between oxygen (a ductus constrictor) and prostaglandins and nitric oxide (ductus dilators) (11,12). Alterations in antenatal glucocorticoid concentrations and postnatal pulmonary vascular resistance also play roles in in vivo ductus constriction (13,14).…”

Avaliação hormonal sérica e estereológica da membrana corioalantóide a termo de éguas: influência no desenvolvimento e nos parâmetros clínicos e metabólicos do potro

“…A maturação e ativação do eixo hipotálamo-hipófise-adrenal do feto e o aumento da secreção de adrenocorticosteróides que ocorre antes do parto na maioria das espécies mamíferas parece exercer um papel central na maturação orgânica do feto (LIGGINS, 1976;BARNES et al, 1978;CLYMAN et al, 1981;SILVER, 1990), proporcionando sua adaptação ao ambiente extra uterino (LIGGINS, 1976).…”

“…A maturação e ativação do eixo hipotálamo-hipófise-adrenal do feto e o aumento da secreção de adrenocorticosteróides que ocorre antes do parto na maioria das espécies mamíferas parece exercer um papel central na maturação final pulmonar e produção de surfactante, maturação renal, aumento das reservas de glicogênio hepático e ativação de sistemas enzimáticos envolvidos na maturação do intestino e até mesmo auxiliar no fechamento dos ductos arteriosos (LIGGINS, 1976;BARNES et al, 1978;CLYMAN et al, 1981;SILVER, 1990), proporcionando a adaptação ao ambiente extra-uterino (LIGGINS, 1976 De acordo com Fowden e Silver (1995) essa mudança da síntese de P 5 para cortisol pelas adrenais fetais na gestação avançada pode desempenhar um importante papel para o início do parto na espécie equina. É proposto que um efeito cumulativo dos progestágenos no final da gestação, principalmente 3β5P, também inibiria a atividade da 3β-HSD nas adrenais fetais, que poderia induzir a uma redução da secreção de corticosteroides por esta glândula, resultando em um subsequente pico do ACTH fetal o que levaria a produção de cortisol (CHAVETTE-PALMER et al, 1997).…”