Interleukin-8, aquaporin-1, and inducible nitric oxide synthase in smoke and burn injured sheep treated with percutaneous carbon dioxide removal

We previously showed that a percutaneous arteriovenous gas exchanger was effective in removing CO₂ and reversing respiratory failure in an ovine model of adult respiratory distress syndrome (ARDS) produced by smoke inhalation and burn injury (Alpard et al., Ann Surg 230:215-224, 1999). In this study, we tested the hypothesis that arteriovenous CO₂ removal (AVCO₂R) lessened endogenous inflammation in the lung. Myeloperoxidase activity, aquaporin-1 (AQP-1), interleukin-8 (IL-8), and inducible nitric oxide synthase mRNAs as well as aquaporin-1, and IL-8 protein were measured in ovine lung tissue. Lung tissue was taken at 96 h (time of sacrifice) from animals with combined smoke inhalation and 40% third degree dermal burn and subsequently treated with AVCO₂R or sham (ventilator alone) after onset of ARDS (PaO₂:FiO₂ ratio of < 200). Myeloperoxidase activity was 1.862 ± 0.302 U/mg protein in the ventilator group and 0.830 ± 0.141 in the AVCO₂R plus ventilator group. AQP-1 mRNA was 140,482 ± 31,702 copies/μg total RNA in the ventilator group and 61,854 ± 22,433 copies/μg total RNA in the AVCO₂R plus ventilator group (p = 0.076). mRNA for IL-8 mRNA in the ventilator alone treated animals was 74,000 ± 3,300 copies/μg total RNA compared to < 1,000 copies/μg total RNA in the ventilator plus AVCO₂R group. This result was highly significant (p < 0.001) Inducible nitric oxide synthase mRNA was 7,853 ± 2,229 copies/μg total RNA for the AVCO₂R group and 5,854 ± 2,070 copies/μg total RNA for the ventilator managed animals. These differences were not statistically significant (p = 0.54). Percutaneous AVCO₂R produced a specific decrease in IL-8 in the smoke and burn injured animals. Furthermore, this effect was consistent with cell signaling mechanisms that increase the expression of IL-8 by cyclic stretching and the observed reduction in the number of neutrophils in the lung parenchyma. Therefore, we speculate that the mechanism by which CO₂ removal exerts a beneficial effect may be due to both decreases in ventilatory requirements, with an accompanying reduction in alveolar stretching, and reduction of neutrophil numbers in lung tissue.