Surfactant plus budesonide decreases lung and systemic inflammation in mechanically ventilated preterm sheep
| Autor: | Gabrielle C. Musk, Augusto F. Schmidt, Alan H. Jobe, Fabrizio Salomone, Emily Royse, Michael W. Clarke, T Brett Kothe, Matthew W. Kemp, Noah H. Hillman |
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| Rok vydání: | 2019 |
| Předmět: |
Pulmonary and Respiratory Medicine
Budesonide medicine.medical_specialty Physiology medicine.medical_treatment Systemic inflammation Gastroenterology Surface-Active Agents 03 medical and health sciences 0302 clinical medicine Pulmonary surfactant 030225 pediatrics Physiology (medical) Internal medicine medicine Animals Lung Mechanical ventilation Inflammation Sheep business.industry Infant Newborn Brain Pulmonary Surfactants Lung Injury Cell Biology Pneumonia respiratory system medicine.disease Respiration Artificial respiratory tract diseases medicine.anatomical_structure 030228 respiratory system Bronchopulmonary dysplasia Animals Newborn Liver medicine.symptom business Research Article medicine.drug |
| Zdroj: | Am J Physiol Lung Cell Mol Physiol |
| ISSN: | 1522-1504 |
| Popis: | Mechanical ventilation with normal tidal volumes (VT) causes lung and systemic inflammation in preterm sheep. Mechanical ventilation is associated with bronchopulmonary dysplasia (BPD) in preterm infants, and the addition of budesonide to surfactant decreases BPD in clinical trials. Budesonide with surfactant will decrease the lung injury from mechanical ventilation for 24 h in preterm sheep. Lambs at 126 ± 1 day gestational age were delivered and randomized to either: 1) surfactant (200 mg/kg) or 2) surfactant mixed with budesonide (0.25 mg/kg) before mechanical ventilation with VT of 7–8 ml/kg for 2, 6, or 24 h ( n = 6 or 7/group). Lung physiology and budesonide levels in the plasma and the lung were measured. Lung tissue, bronchoalveolar lavage fluid (BALF), liver, and brain tissues were evaluated for indicators of injury. High initial budesonide plasma levels of 170 ng/ml decreased to 3 ng/ml at 24 h. Lung tissue budesonide levels were less than 1% of initial dose by 24 h. Although physiological variables were generally similar, budesonide-exposed lambs required lower mean airway pressures, had higher hyperoxia responses, and had more stable blood pressures. Budesonide decreased proinflammatory mRNA in the lung, liver, and brain. Budesonide also decreased total protein and proinflammatory cytokines in BALF, and decreased inducible nitric oxide synthase activation at 24 h. In ventilated preterm lambs, most of the budesonide left the lung within 24 h. The addition of budesonide to surfactant improved physiology, decreased markers of lung injury, and decreased systemic responses in liver and brain. |
| Databáze: | OpenAIRE |
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