Chronic lung injury in preterm lambs. Disordered respiratory tract development

Area of Science:

• Neonatal Physiology
• Pulmonary Medicine
• Animal Models of Disease

Background:

• Bronchopulmonary dysplasia (BPD) is a significant cause of chronic lung disease in preterm infants.
• The exact causes of BPD are not fully understood, and a lack of reliable large-animal models has hindered research.
• Previous studies have been limited in their ability to fully replicate the complex lung pathology of BPD.

Purpose of the Study:

• To develop and validate a large-animal model of BPD in preterm lambs.
• To compare the histopathology of lung injury in this lamb model with that observed in human infants with BPD.
• To investigate the influence of different mechanical ventilation strategies, specifically tidal volume (VT), on lung injury outcomes.

Main Methods:

• Preterm lambs (125 ± 4 days gestation) were mechanically ventilated for 3–4 weeks post-birth.
• Two ventilation strategies were employed: slow, deep ventilation (20 breaths/min, 15 ± 2 ml/kg VT) and rapid, shallow ventilation (60 breaths/min, 6 ± 1 ml/kg VT).
• Quantitative histologic analysis was performed and compared to age-matched control lambs (term newborns and 3–4 week old term lambs).

Main Results:

• Mechanically ventilated preterm lambs exhibited lung abnormalities including nonuniform inflation, impaired alveolar formation, altered elastin, increased bronchiolar muscularization, inflammation, and edema.
• These histopathologic changes closely resembled those found in preterm infants who died with BPD.
• Slow, deep ventilation resulted in less atelectasis and alveolar formation but more elastin compared to rapid, shallow ventilation.

Conclusions:

• Prolonged mechanical ventilation of preterm lambs effectively models the pulmonary histopathology of BPD seen in human infants.
• The development of BPD in this model is not prevented by surfactant therapy and does not require hyperoxia.
• Tidal volume is a significant factor influencing the histopathologic outcome in this BPD model.