Combined effects of fetal beta agonist stimulation and glucocorticoids on lung function of preterm lambs.
We asked whether a single-dose fetal treatment strategy using betamethasone plus either a long-acting beta 2 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 beta-methasone 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 beta 2 agonist system did not augment postnatal lung function significantly above that noted for betamethasone alone with the agents, doses, and duration of exposures tested.
Jobe
A H
AH
Department of Pediatrics, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance, USA.
Ikegami
M
M
Padbury
J
J
Polk
D H
DH
Korirnilli
A
A
Gonzales
L W
LW
Ballard
P L
PL
D015056:1-Methyl-3-isobutylxanthine / Q000008:administration & dosage / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D003994:Bucladesine / Q000008:administration & dosage / Q000494:pharmacology*; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011510:Proteolipids / Q000187:drug effects; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000187:drug effects; D012756:Sheep
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D005938:Glucocorticoids; D010726:Phosphodiesterase Inhibitors; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D003994:Bucladesine; D001623:Betamethasone; D064429:Fatty Acid Synthases; D015056:1-Methyl-3-isobutylxanthine; D000068759:Formoterol Fumarate