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 (AVCO(2)R) 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 AVCO(2)R or sham (ventilator alone) after onset of ARDS (PaO2:FiO(2) ratio of < 200). Myeloperoxidase activity was 1.862 +/- 0.302 U/mg protein in the ventilator group and 0.830 +/- 0.141 in the AVCO(2)R plus ventilator group. AQP-1 mRNA was 140,482 +/- 31,702 copies/mug total RNA in the ventilator group and 61,854 +/- 22,433 copies/mug total RNA in the AVCO(2)R plus ventilator group (p 0.076). mRNA for IL-8 mRNA in the ventilator alone treated animals was 74,000 +/- 3,300 copies/mug total RNA compared to < 1,000 copies/mug total RNA in the ventilator plus AVCO(2)R group. This result was highly significant (p < 0.001) Inducible nitric oxide synthase mRNA was 7,853 <plus/minus> 2,229 copies/mug total RNA for the AVCO(2)R group and 5,854 +/- 2,070 copies/mug total RNA for the ventilator managed animals. These differences were not statistically significant (p = 0.54). Percutaneous AVCO(2)R 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.