Oxygen-mediated parenchymal and vascular lung injury

摘要

Bronchopulmonary dysplasia (BPD) remains an important cause of morbidity and mortality in premature infants receiving intensive care. Pulmonary O_2 toxicity, through the generation of reactive oxygenitrogen species in excessuf antioxidant defenses, is believed to be a major contributor to the development of BPD. Our studies demonstrated that hyperoxia-induced lung epithelial cell death is a necrosis secondary to loss of reduced thiols, and is hydrogen peroxide-dependent In vitro. Parenchymal injury in vivo also appears to be hydrogen peroxide-dependent and is alveolar macrophage- independent, whereas pulmonary hypertension appears to be isoprostane-, endothelin 1- (ET-1) and alveolar macrophage-dependent. An antioxidant intervention prevented pulmonary hypertension but not the changes in lung architecture found in animals exposed to oxygen. This indicates that different mediators regulate these different aspects of pulmonary oxygen toxicity. Antioxidant interventions can have an adverse impact on lung growth, which is in keeping with the increasingly recognized role of low levels of oxygen-derived products in normal cell growth. Antioxidant interventions may not, therefore, be an appropriate therapy in the newborn infant. The recognition of the importance of ET-1 and 8-isoprostane in oxygen-mediated pulmonary hypertension and of neutrophils in parenchymal injury, and their reversibility with appropriate interventions, suggests that alternative approaches may be feasible.