A Premature Rabbit Kitten Model for Evaluation of Bronchopulmonary Dysplasia Therapies Reproduces Myeloperoxidase-Associated Pathology and Therapeutic Responses

Myeloperoxidase (MPO) plays a significant role in the development and progression of bronchopulmonary dysplasia (BPD). The neonatal rat model has shown that the tripeptide N-acetyl-lysyltyrosylcysteine amide (KYC) attenuates hyperoxia-induced BPD-like injury, in part by reducing MPO-mediated toxic oxidants and additional cytoprotective mechanisms. However, the rat model does not fully replicate the key characteristics of surfactant deficiency and immature antioxidant capacity in premature human neonates. In contrast, premature rabbit kittens share key features with those of premature human neonates. For this study, premature rabbit kittens delivered at 29 days of gestation (term is 31 days) were exposed to 95% oxygen for 7 days. Hyperoxia caused a BPD-like phenotype characterized by increased MPO-positive inflammatory cell infiltration, elevated MPO expression, alveolar simplification, septal wall thickening, and pulmonary arterial medial wall thickening. Daily intraperitoneal KYC administration attenuated lung inflammatory cell infiltration, reduced MPO expression, improved alveolar morphometric indices, and mitigated pulmonary arterial medial wall thickening compared with phosphate-buffered saline treatment. There were no significant differences in weight changes or survival between the groups. These findings demonstrate that premature rabbit kittens provide a useful developmental model for the evaluation of candidate BPD therapies and reproduce MPO-associated pathological and therapeutic responses previously observed in neonatal rat studies.