A Rat Model for Arrest of Alveolarization Induced by Antenatal Endotoxin Administration

A possible association between intrauterine inflammation and impairments of lung development has been suggested. The purpose of this study is to determine the influence of a potent proinflammatory agent, intra-amniotic lipopolysaccharide (LPS), on lung development. At 21 d gestation, an intra-amniotic injection of 1 μg LPS was administered to two subgroups of WKAH rats. One subgroup received only LPS and the other received LPS plus a fetal intraperitoneal dose of 0.25 μg granulocyte-colony stimulating factor (hrG-CSF) to produce peripheral blood neutrophilia. A third subgroup received hrG-CSF only, and a control group received maternal intraamniotic and fetal intraperitoneal normal saline. All pups were delivered by cesarean section at 22 d (term, 22.5 d) and maintained under identical conditions. Left upper lungs were obtained for morphometric analysis at 1, 3, 7, 14, 21, 45, and 60 d of age. Morphometric analysis indicated that changes in alveolar surface density ( Sv ), average alveolar radius ( r ), and numerical density of alveoli ( nv ) all showed that there were fewer and larger alveoli in rat lungs that had been exposed to LPS, but not to hrG-CSF alone or saline. LPS-exposed alveoli showed fewer secondary septa, suggesting an arrest of alveolarization. No destructive changes were observed in any alveoli. We concluded that these changes could be caused purely by intra-amniotic LPS. These abnormalities closely mimic those of new bronchopulmonary dysplasia. The LPS damage model may be applicable to further studies of the pathophysiology of new BPD.