Inhibition of apoptosis by 60% oxygen: a novel pathway contributing to lung injury in neonatal rats.

During early postnatal alveolar formation, the lung tissue of rat pups undergoes a physiological remodeling involving apoptosis of distal lung cells. Exposure of neonatal rats to severe hyperoxia (≥95% O(2)) both arrests lung growth and results in increased lung cell apoptosis. In contrast, exposure to moderate hyperoxia (60% O(2)) for 14 days does not completely arrest lung cell proliferation and is associated with parenchymal thickening.

Therapeutic effects of hypercapnia on chronic lung injury and vascular remodeling in neonatal rats.

Permissive hypercapnia, achieved using low tidal volume ventilation, has been an effective protective strategy in patients with acute respiratory distress syndrome. To date, no such protective effect has been demonstrated for the chronic neonatal lung injury, bronchopulmonary dysplasia. The objective of our study was to determine whether evolving chronic neonatal lung injury, using a rat model, is resistant to the beneficial effects of hypercapnia or simply requires a less conservative approach to hypercapnia than that applied clinically to date.

A critical role for the IL-1 receptor in lung injury induced in neonatal rats by 60% O2.

IL-1 beta, a proinflammatory cytokine, may contribute to the development of the chronic neonatal lung injury, bronchopulmonary dysplasia. Chronic neonatal lung injury was induced in rats, by exposure to 60% O2 for 14 d from birth, to determine whether pulmonary IL-1 expression was up-regulated and, if so, whether a daily s.c.

A critical role for fibroblast growth factor-7 during early alveolar formation in the neonatal rat.

Mesenchymal cell-derived FGF-7 (fibroblast growth factor-7) induces proliferation in both epithelial and endothelial cells. We found FGF-7 to be expressed in the lungs of neonatal rats from birth to d 14 of age. A role for FGF-7 in early postnatal lung growth and alveolar formation, by an action on type II pneumocytes, has been excluded by the work of others.

Fibroblast growth factor-2 and receptor-1alpha(IIIc) regulate postnatal rat lung cell apoptosis.

Rationale: Fibroblast growth factor receptor-1alpha(IIIc) [FGF-R1alpha(IIIc)] regulates recovery of neonatal rat lung growth, after 95% oxygen-mediated growth arrest. Its role in normal postnatal alveologenesis is unknown.

Objective: To determine if FGF-R1alpha(IIIc) regulates normal postnatal alveologenesis.

Hepatocyte growth factor is required for alveologenesis in the neonatal rat.

Rationale: Our core hypothesis is that growth factors that have dysregulated expression during experimental neonatal lung injury are likely to be involved in normal postnatal lung growth and alveologenesis.

Objectives: To determine if hepatocyte growth factor (HGF) is upregulated in neonatal lung injury and is essential for postnatal alveologenesis.

Methods: A neonatal lung injury, in which there were patchy areas of interstitial thickening with a relative increase in the proportion of epithelial cells, was induced in newborn rats by exposing them to 60% oxygen for 14 days.

Opposing effects of 60% oxygen and neutrophil influx on alveologenesis in the neonatal rat.

The lungs of newborn rats exposed to 60% oxygen for 14 days develop an injury that shares morphologic similarities to human bronchopulmonary dysplasia (BPD). Neutrophil influx into the lung, as part of an inflammatory response, may play a pivotal role in the development of BPD. A neutrophil chemokine, cytokine-induced neutrophil chemoattractant-1, which signals through the neutrophil CXC chemokine receptor-2, is increased in the lung tissue of newborn rats exposed to 60% oxygen.