Ventilation strategy affects cytokine release after mesenteric ischemia-reperfusion in rats

Objective: To evaluate the impact of different ventilation modalities on lung and plasma concentrations of cytokines in a model of secondary lung inflammation, mesenteric ischemia-reperfusion, in rats. Design. Prospective, randomized, controlled animal study. Setting: Research laboratory of a university. Subjects. Sixty-four male adult Wistar rats weighing 320-380 g. Interventions., Eight groups were studied. Two groups underwent no surgical procedure: They were either not ventilated or ventilated with an injurious modality consisting of 30 mL/kg tidal volume (VT) without positive-end expiratory pressure (PEEP). Animals of the other groups underwent laparotomy with or without 2-hr mesenteric ischemia followed by 4 hrs of reperfusion during which the rats were mechanically ventilated. Ventilation modalities were conventional (tidal volume 10 mL/kg, PEEP 3 cm H2O), protective (6 mL/kg, 6 cm H2O), or injurious (tidal volume 30 mL/kg and no PEEP). Rats were killed by exsanguination, and their lungs were excised and homogenized in buffer. Supernatants of lung homogenates and plasmas were stored at -80degreesC for subsequent measurements. Measurements and Main Results. Tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, macrophage inhibitory protein 2, and interleukin-10 were determined in lung supernatants and plasmas with a rat-specific enzyme-linked immunosorbent assay. Lung and plasma cytokine concentrations were not significantly different between rats ventilated with the injurious modality only. and nonventilated rats. Lung and plasma cytokine concentrations were higher in rats that had undergone mesenteric ischemia-reperfusion than in rats with laparotomy only, whatever ventilation modality. Lung and plasma cytokine concentrations were higher in these rats after the injurious ventilation modality than after the other modalities. Conclusion. This study shows that an injurious ventilation does not produce significant in vivo release of cytokines in intact animals but promotes the release of pro- and anti-inflammatory cytokines in an inflammatory context.