Moderate tidal volumes and oxygen exposure during initiation of ventilation in preterm fetal sheep

Background: Preterm infants often receive mechanical ventilation and oxygen at birth. Exposure to large tidal volumes (V_T s) at birth causes lung inflammation, and oxygen may amplify the injury. We hypothesized that normal V_T ventilation at birth causes lung injury that is exacerbated by 95% oxygen. Methods: The head and chest of anesthetized preterm fetal sheep (129 ± 1 d gestation) were surgically exteriorized while maintaining the placental circulation. Fetuses were randomized to four groups with either V _T ventilation to 6 ml/kg or continuous positive airway pressure of 5 cm H₂ O, and either 95%O 2/5%CO₂ or 95%N 2/5%CO ₂. Age-matched fetuses were used as controls. After a 15-min intervention, the fetal lamb was returned to the uterus for ¹h 45 min.Results:In ventilated lambs, V_T was 6.2 ± 0.4 ml/kg at 15 min. Ventilation increased proinflammatory cytokines as compared with controls and lambs on continuous positive airway pressure, with recruitment of primarily monocytes to bronchoalveolar lavage fluid. Early response protein 1 was activated around the bronchioles in V_T-ventilated animals. The 15-min oxygen exposure did not change inflammatory mediators or other markers of lung and oxidative stress. Conclusion: A V_T of 6-7 ml/kg at birth increased early markers of injury and lung inflammation. Brief exposure to 95% oxygen did not alter lung inflammation.