Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs

BACKGROUND: Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP) is being increasingly used clinically to transition preterm infants at birth. OBJECTIVE: To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs. METHODS: The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH(2)O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH(2)O animal served as controls. Fetal lung fluid (FLF), bronchoalveolar lavage fluid (BAL), right mainstem bronchi and peripheral lung tissue were evaluated for inflammation. RESULTS: Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH(2)O to 2.4±0.3 mL/kg at 16 cmH(2)O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used. CONCLUSION: Distending pressures as high as 16 cmH(2)O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.