Chronic lung injury in preterm lambs - Disordered respiratory tract development

The cause of chronic lung disease of early infancy, often called bronchopul monary dysplasia (BPD), remains unclear, partly because large-animal models that reliably reproduce BPD have not been available. We developed a model of BPD in lambs that are delivered prematurely and ventilated for 3 to 4 wk after birth to determine whether the histopathology of chronic lung injury in premature lambs mimics that which occurs in preterm infants who die wit h BPD, and to compare two ventilation strategies to test the hypothesis tha t differences in tidal volume (VT) influence histopathologic outcome. The t wo ventilation strategies were slow, deep ventilation (20 breaths/min, 15 /- 2 ml/kg body weight VT; n = 5) or rapid, shallow ventilation (60 breaths /min, 6 +/- 1 ml/kg body weight VT; n = 5). Lambs were delivered at 125 +/- 4 d gestation (term = 147 d), treated with surfactant, and mechanically ve ntilated with sufficient supplemental oxygen to maintain normal arterial ox ygenation (60 to 90 mm Hg). Quantitative histologic analysis revealed lung structural abnormalities for both groups of experimental lambs compared wit h lungs of control term lambs that were < 1 d old (matched for developmenta l age; n = 5) or 3 to 4 wk old (matched for postnatal age; n = 5). Compared with control lambs, chronically ventilated preterm lambs had pulmonary his topathology characterized by nonuniform inflation patterns, impaired alveol ar formation, abnormal abundance of elastin, increased muscularization of t erminal bronchioles, and inflammation and edema. Slow, deep ventilation was associated with less atelectasis, less alveolar formation, and more elasti n when compared with rapid, shallow ventilation. We conclude that prolonged mechanical ventilation of preterm lambs disrupts lung development and prod uces pulmonary histopathologic changes that are very similar to those that are seen in the lungs of preterm infants who die with BPD. This chronic lun g disease is not prevented by surfactant replacement at birth, does not app ear to require arterial hyperoxia, and is influenced by VT.