Mitochondrial function in lungs of rats with different susceptibilities to hyperoxia-induced acute lung injury.

Adult rats exposed to hyperoxia (>95% O) die from respiratory failure in 60-72 h. However, rats preconditioned with >95% O for 48 h followed by 24 h in room air acquire tolerance of hyperoxia (H-T), whereas rats preconditioned with 60% O for 7 days become more susceptible (H-S). Our objective was to evaluate lung tissue mitochondrial bioenergetics in H-T and H-S rats. Bioenergetics was assessed in mitochondria isolated from lung tissue of H-T, H-S, and control rats. Expressions of complexes involved in oxidative phosphorylation (OxPhos) were measured in lung tissue homogenate. Pulmonary endothelial filtration coefficient () and tissue mitochondrial membrane potential (Δψ) were evaluated in isolated perfused lungs (IPLs). Results show that ADP-induced OxPhos capacity () decreased in H-S mitochondria but increased in H-T. Δψ repolarization time following ADP-stimulated depolarization increased in H-S mitochondria. Complex I expression decreased in H-T (38%) and H-S (43%) lung homogenate, whereas complex V expression increased (70%) in H-T lung homogenate. Δψ is unchanged in H-S and H-T lungs, but complex II has a larger contribution to Δψ in H-S than H-T lungs. increased in H-S, but not in H-T lungs. For H-T, increased complex V expression and counter the effect of the decrease in complex I expression on Δψ. A larger complex II contribution to Δψ along with decreased and increased could make H-S rats more hyperoxia susceptible. Results are clinically relevant since ventilation with ≥60% O is often required for extended periods in patients with acute respiratory distress syndrome (ARDS). We assessed lung tissue mitochondrial bioenergetics in rats with tolerance (H-T) or susceptibility (H-S) to hyperoxia-induced ARDS. Results from studies in isolated mitochondria, tissue homogenate, and isolated perfused lungs show that mitochondrial bioenergetics are differentially altered in H-T and H-S lungs suggesting a potential role for mitochondrial bioenergetics in hyperoxia-induced ARDS. Results are clinically relevant since hyperoxia exposure is a primary therapy for patients with ARDS, and differential sensitivity to hyperoxia surely occurs in humans.