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In study, we investigated the effects of different tidal volumes on cerebral tissue oxygenation and cerebral metabolism in a porcine model of acute lung injury (ALI). We hypothesized that mechanical ventilation with low tidal (LT) volumes improves cerebral tissue oxygenation and metabolism after experimentally induced ALI.After inducing experimental ALI by surfactant depletion, we studied two conditions in 10 female pigs: 1) LT volume ventilation with 6 mL/kg body weight, and 2) high tidal (HT) volume ventilation with 12 mL/kg body weight. Variables of gas exchange, hemodynamic, continuous cerebral tissue oxygen tension (ptiO2), cerebral microdialysis, and systemic cytokines were analyzed. After induction of ALI, data were collected at 2, 4, and 8 h. The primary end point was the change in ptiO2. For group comparisons, a t-test was used. A value of <0.05 was considered to indicate statistical significance.At baseline and after induction of ALI, no differences between groups were found in ptiO2; however, ptiO2 was significantly lower in the HT group after 4 and 8 h. Pao2 and Paco2 showed no significant differences between the groups at all timepoints. Regarding cerebral microdialysis, a significantly higher level of extracellular lactate could be demonstrated after 2, 4, and 8 h in the HT group. The release of cytokines resulted in higher values for interleukin-6 and interleukin-8 in the HT group.Protective ventilation with LT yielded a significant improvement in cerebral tissue oxygenation and metabolism compared to HT ventilation in a porcine model of ALI. There was dissociation between arterial and cerebral tissue oxygenation. Cerebral oxygenation and metabolism might have possibly been impaired by a more distinctive inflammatory response in the HT group.