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Budesonide with surfactant decreases systemic responses in mechanically ventilated preterm lambs exposed to fetal intra-amniotic lipopolysaccharide.
- Source :
-
Pediatric research [Pediatr Res] 2021 Aug; Vol. 90 (2), pp. 328-334. Date of Electronic Publication: 2020 Nov 11. - Publication Year :
- 2021
-
Abstract
- Background: Chorioamnionitis is associated with increased rates of bronchopulmonary dysplasia (BPD) in ventilated preterm infants. Budesonide when added to surfactant decreased lung and systemic inflammation from mechanical ventilation in preterm lambs and decreased the rates and severity of BPD in preterm infants. We hypothesized that the addition of budesonide to surfactant will decrease the injury from mechanical ventilation in preterm lambs exposed to intra-amniotic (IA) lipopolysaccharide (LPS).<br />Methods: Lambs at 126 ± 1 day GA received LPS 10 mg IA 48 h prior to injurious mechanical ventilation. After 15 min, lambs received either surfactant mixed with: (1) saline or (2) Budesonide 0.25 mg/kg, then ventilated with normal tidal volumes for 4 h. Injury markers in the lung, liver, and brain were compared.<br />Results: Compared with surfactant alone, the addition of budesonide improved blood pressures, dynamic compliance, and ventilation, while decreasing mRNA for pro-inflammatory cytokines in the lung, liver, and multiple areas of the brain. LPS caused neuronal activation and structural changes in the brain that were not altered by budesonide. Budesonide was not retained within the lung beyond 4 h.<br />Conclusions: In preterm lambs exposed to IA LPS, the addition of budesonide to surfactant improved physiology and markers of lung and systemic inflammation.<br />Impact: The addition of budesonide to surfactant decreases the lung and systemic responses to injurious mechanical ventilation preterm lambs exposed to fetal LPS. Budesonide was present in the plasma by 15 min and the majority of the budesonide is no longer in the lung at 4 h of ventilation. IA LPS and mechanical ventilation caused structural changes in the brain that were not altered by short-term exposure to budesonide. The budesonide dose of 0.25 mg/kg being used clinically seems likely to decrease lung inflammation in preterm infants with chorioamnionitis.<br /> (© 2020. International Pediatric Research Foundation, Inc.)
- Subjects :
- Animals
Brain drug effects
Brain metabolism
Brain physiopathology
Bronchopulmonary Dysplasia etiology
Bronchopulmonary Dysplasia metabolism
Bronchopulmonary Dysplasia physiopathology
Chorioamnionitis chemically induced
Chorioamnionitis metabolism
Chorioamnionitis physiopathology
Cytokines metabolism
Disease Models, Animal
Drug Therapy, Combination
Female
Fetal Diseases etiology
Fetal Diseases metabolism
Fetal Diseases physiopathology
Gestational Age
Inflammation Mediators metabolism
Lipopolysaccharides
Lung metabolism
Lung physiopathology
Pneumonia etiology
Pneumonia metabolism
Pneumonia physiopathology
Pregnancy
Respiration, Artificial adverse effects
Sheep, Domestic
Systemic Inflammatory Response Syndrome etiology
Systemic Inflammatory Response Syndrome metabolism
Systemic Inflammatory Response Syndrome physiopathology
Biological Products pharmacology
Bronchopulmonary Dysplasia prevention & control
Budesonide pharmacology
Chorioamnionitis drug therapy
Fetal Diseases prevention & control
Glucocorticoids pharmacology
Lung drug effects
Phospholipids pharmacology
Pneumonia prevention & control
Pulmonary Surfactants pharmacology
Systemic Inflammatory Response Syndrome prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0447
- Volume :
- 90
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Pediatric research
- Publication Type :
- Academic Journal
- Accession number :
- 33177678
- Full Text :
- https://doi.org/10.1038/s41390-020-01267-8