Postnatal hypoxic preconditioning attenuates lung damage from hyperoxia in newborn mice

Autores de IIS La Fe

• Iván Millán Yáñez

  Autor

• Máximo Vento Torres

  Autor

• María Isabel Torres Cuevas

  Autor

Participantes ajenos a IIS La Fe

• Pérez, S
• Rius-Pérez, S
• Asensi, MA
• García-Verdugo, JM

Grupos

• Perinatología

Abstract

BackgroundPreterm infants frequently require oxygen supplementation at birth. However, preterm lung is especially sensible to structural and functional damage caused by oxygen free radicals.MethodsThe adaptive mechanisms implied in the fetal-neonatal transition from a lower to a higher oxygen environment were evaluated in a murine model using a custom-designed oxy-chamber. Pregnant mice were randomly assigned to deliver in 14% (hypoxic preconditioning group) or 21% (normoxic group) oxygen environment. Eight hours after birth FiO2 was increased to 100% for 60 min and then switched to 21% in both groups. A control group remained in 21% oxygen throughout the study.ResultsMice in the normoxic group exhibited thinning of the alveolar septa, increased cell death, increased vascular damage, and decreased synthesis of pulmonary surfactant. However, lung histology, lamellar bodies microstructure, and surfactant integrity were preserved in the hypoxic preconditioning group after the hyperoxic insult.ConclusionPostnatal hyperoxia has detrimental effects on lung structure and function when preceded by normoxia compared to controls. However, postnatal hypoxic preconditioning mitigates lung damage caused by a hyperoxic insult.ImpactHypoxic preconditioning, implemented shortly after birth mitigates lung damage caused by postnatal supplemental oxygenation.The study introduces an experimental mice model to investigate the effects of hypoxic preconditioning and its effects on lung development. This model enables researchers to delve into the intricate processes involved in postnatal lung maturation.Our findings suggest that hypoxic preconditioning may reduce lung parenchymal damage and increase pulmonary surfactant synthesis in reoxygenation strategies during postnatal care.

© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.

Keywords

• Animals; Animals, Newborn; Disease Models, Animal; Female; Hyperoxia; Hypoxia; Lung; Mice; Mice, Inbred C57BL; Oxygen; Pregnancy; Pulmonary Surfactants; adenosine triphosphate; lactic acid; lung surfactant; oxygen; pentobarbital; RNA; lung surfactant; animal experiment; animal model; animal tissue; Article; blood vessel injury; brain level; cell death; controlled study; fetus lung maturation; fraction of inspired oxygen; histology; hyperoxia; hypoxia; immunohistochemistry; lactate blood level; lamellar body; lung development; lung injury; lung parenchyma; lung structure; mouse; nonhuman; oxygen saturation; oxygenation; postnatal care; prematurity; real time polymerase chain reaction; reoxygenation; RNA isolation; Western blotting; animal; C57BL mouse; complication; disease model; female; lung; metabolism; newborn; pathology; pathophysiology; pregnancy