Combined Effects of Fetal Beta Agonist Stimulation and Glucocorticoids on Lung Function of Preterm Lambs

Abstract

We asked whether a single-dose fetal treatment strategy using betamethasone plus either a long-acting beta2 agonist (formoterol) or betamethasone plus agents that elevate intracellular cyclic adenosine monophosphate (isobutyl methylxanthine and dibutyryl-cyclic adenosine monophosphate) would augment the effects of prenatal betamethasone on postnatal lung function. Preterm lambs were treated with 0.5 mg/kg betamethasone or betamethasone plus the other agents and delivered 48 h after treatment. The postnatal lung function as assessed by compliance, ventilatory efficiency, and lung volumes at 40 min of age was improved by prenatal betamethasone and improved further by combination treatment, although the augmented responses were not significantly greater than with betamethasone alone. Fatty acid synthase protein and enzymatic activity were not increased by betamethasone or combined treatments, in contrast to responses reported for other animal models. There were no effects of glucocorticoids or the combined treatments on surfactant. Stimulation of the beta2 agonist system did not augment postnatal lung function significantly above that noted for betamethasone alone with the agents, doses, and duration of exposures tested.

Antenatal Terbutaline Administration Decreases the Lung Hyaluronan Concentration in Preterm Rabbit Pups

“…The observed absence of a further effect of the combined exposure to betamethasone and terbutaline as compared to that obtained after exposure to betamethasone only might indicate that a maximal response was attained with exposure to the corticosteroid alone. This is in agreement with the finding by Jobe et al [21] in a study of preterm lambs that postnatal lung function was improved by prenatal betamethasone, but not significantly improved further by a combination of treatment with betamethasone and ß-agonist stimulation.…”

“…This increase in concentration can be accelerated by corticosteroids [19,20]. Stimulation of ß-adrenergic receptors elevates intracellular cAMP, thereby increasing the mRNA levels for surfactant proteins and lipogenic enzymes such as fatty acid synthase [21]. ß-adrenergic agonists have also been shown to induce surfactant secretion and may stimulate surfactant synthesis and recycling in vivo [5,6].…”

Elective Cesarean Section: Its Impact on Neonatal Respiratory Outcome

“…Glucocorticoids have also been shown to enhance the responsiveness of lungs to β-adrenergic agents and thyroid hormones. 74 The enhanced sodium reabsorption induced by glucocorticoids can be blocked by amiloride, suggesting a role for ENaC. This effect was not observed with triiodothyronine (T3) or with cAMP.…”

“…70 In addition, steroids have been shown to have beneficial effects on the surfactant system as well as pulmonary mechanics. 43,74,111,121,133,134 …”

Clinical implication of lung fluid balance in the perinatal period

“…59,60 Glucocorticosteroids also increase the number of available sodium channels by increasing ENaC trafficking and decreasing the rate of degradation of existing channels 61,62 and improving lung responsiveness to b2 stimulants and thyroid hormones. 63 Stutchfield et al 64 have shown that two doses of betamethasone given 48 h before cesarean section significantly decreased admissions due to respiratory distress. It was also shown that preterm babies whose mothers received betamethasone had shown improvement in pulmonary adaptation, 65 presumably reflecting improved fetal lung fluid clearance.…”