Mechanical ventilation (MV) of newborn mice for 24 h leads to reduced VEGF receptor‐2 (VEGFR2) and tenascin‐C (TNC) proteins, enlarged airspaces and increased lung elastin (Eln)

We previously showed that MV of newborn mice with 40% O 2 for 8 h decreased lung expression of genes (VEGF, its receptor VEGFR2, TNC) that affect formation of alveoli and lung capillaries. MV with 40% O 2 or air for 8 h increased lung expression of genes (tropoelastin, lysyl oxidase) that regulate elastin (Eln) synthesis. As lung septation and angiogenesis occur mainly after term birth in mice, we did studies to see if MV with 40% O 2 for 24 h would affect lung content of specific proteins (VEGF, VEGFR2, TNC, Eln) and induce structural changes in alveoli and Eln. We studied 2 groups of 4 d old mice that weighed 2–4 g: group 1 had MV with 40% O 2 at 180 breaths/min via tracheostomy, group 2 had sham surgery and then breathed 40% O 2 for 24 h. Some lungs (4–6/grp) were frozen for immunoblot protein assay, others (6–8/grp) were instilled with fixative at 20 cmH 2 O, immersed in fluid for volume measurements, and processed for histology, analysis of alveolar structure and Eln deposition (Hart's stain). VEGFR2 and TNC protein content was reduced in lungs of pups that had MV vs controls. Histology showed little or no injury. Lung volume was 154 ± 17 μl in pups that had MV vs 162 ± 11 μl in controls. Airspace size was greater after 24 h of MV than in controls. MV led to a 50% increase in lung Eln, which was widely dispersed rather than normally localized at septal tips. We conclude that prolonged cyclic stretch with O 2 ‐rich gas at a critical stage of lung development reduces abundance of proteins that regulate formation of alveoli and lung capillaries, and causes structural changes that may impair lung function. Funded by: NIH RO1 HL62512 and P50 HL56401