Time course of hypoxia-induced lung injury in rats

We investigated the effects of normobaric hypoxia on rat lungs and hypothesized that the hypoxic exposure would induce lung injury with pulmonary edema and inflammation ensued by development of fibrosis. Rats were exposed to 10% O2 in nitrogen over 6–168 h. We analyzed cardiovascular function and pulmonary changes, lung histology and mRNA expression of extracellular matrix (ECM) molecules in the lung. Significant hemodynamic changes occurred after 168 h of hypoxic exposure. Moderate pulmonary edema appeared after 8 h and peaked after 16 h of hypoxia. It was accompanied by inflammation, fibrosis and vascular hypertrophy. mRNA expression of transforming growth factor-β2 and -β3 was up-regulated in lung tissue after 8 h of hypoxia. After 8–16 h, mRNA expression of collagen types I and III and of other ECM molecules was significantly elevated and increased further with longer exposure to hypoxia. The time course of hypoxia-induced pulmonary injury resembled that previously observed after continuous norepinephrine infusion in rats.