Hypercapnic acidosis minimizes endotoxin-induced gut mucosal injury in rabbits

Objective  Recent evidence demonstrated that hypercapnic acidosis due to lung protective strategy was not only permissive but also even therapeutic for injured lung. Since the effects of hypercapnic acidosis on extra-pulmonary organs remain to be clarified, we tested the hypothesis that hypercapnic acidosis protects gut mucosal barrier function by modulating inflammation in a rabbit model of endotoxemia. Design  Prospective randomized animal study. Setting  University research laboratory. Subjects  Male New Zealand white rabbits. Interventions  Thirty-two animals were randomly allocated into two groups: normocapnia (n = 17) and hypercapnia (n = 15). The latter group received F_ICO₂ 5% under mechanical ventilation to achieve hypercapnia throughout the study periods, whereas the former with F_ICO₂ 0%. Measurements and results  Arterial blood gas, intramucosal pH (pHi) and portal blood flow were assessed at baseline, 2-h and 4-h infusion of lipopolysaccharide. At 4 h, ileal myeloperoxidase (MPO) activity and intestinal permeability were measured. The animals in the hypercapnia group showed apparent hypercapnic acidosis and progressive intramucosal acidosis at 4 h, accompanied by significantly lower intestinal permeability versus normocapnia group. Ileal MPO activity was comparable between the study groups. Conclusions  Hypercapnic acidosis attenuates endotoxin-induced gut barrier dysfunction possibly through neutrophil-independent mechanisms. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.