Surfactant plus budesonide decreases lung and systemic responses to injurious ventilation in preterm sheep
| Autor: | Erin L. Fee, Alan H. Jobe, Fabrizio Salomone, Noah H. Hillman, Augusto F. Schmidt, Matthew W. Kemp, Michael W. Clarke, T Brett Kothe, Gabrielle C. Musk, Emily Royse |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Budesonide Physiology medicine.medical_treatment Gestational Age Lung injury Surfactant therapy Positive-Pressure Respiration 03 medical and health sciences 0302 clinical medicine Pulmonary surfactant Pregnancy Physiology (medical) medicine Tidal Volume Animals Humans RNA Messenger Lung Mechanical ventilation Sheep business.industry Respiration Infant Newborn Pulmonary Surfactants Cell Biology Lung Injury Pneumonia respiratory system Respiration Artificial respiratory tract diseases 030104 developmental biology medicine.anatomical_structure 030228 respiratory system Animals Newborn Liver Anesthesia Breathing Cytokines Premature Birth Female business medicine.drug Research Article |
| Zdroj: | Am J Physiol Lung Cell Mol Physiol |
| Popis: | Mechanical ventilation from birth with normal tidal volumes (VT) causes lung injury and systemic responses in preterm sheep. The addition of budesonide to surfactant therapy decreases these injury markers. Budesonide and surfactant will decrease the injury from injurious VT ventilation in preterm sheep. Lambs at 126 ± 1 day gestational age were ventilated from birth with either: 1) Normal VT [surfactant 200 mg/kg before ventilation, positive end expiratory pressure (PEEP) 5 cmH2O, VT 8 mL/kg] or 2) Injury VT (high pressure, 100% oxygen, no PEEP) for 15 min, then further randomized to surfactant + saline or surfactant + 0.25 mg/kg budesonide with Normal VT for 6 h. Lung function and lung, liver, and brain tissues were evaluated for indicators of injury. Injury VT + saline caused significant injury and systemic responses, and Injury VT + budesonide improved lung physiology. Budesonide decreased lung inflammation and decreased pro-inflammatory cytokine mRNA in the lung, liver, and brain to levels similar to Normal VT + saline. Budesonide was present in plasma within 15 min of treatment in both ventilation groups, and less than 5% of the budesonide remained in the lung at 6 h. mRNA sequencing of liver and periventricular white matter demonstrated multiple pathways altered by both Injury VT and budesonide and the combination exposure. In lambs receiving Injury VT, the addition of budesonide to surfactant improved lung physiology and decreased pro-inflammatory cytokine responses in the lung, liver, and brain to levels similar to lambs receiving Normal VT. |
| Databáze: | OpenAIRE |
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