Effect of Hypercapnia on Murine Ventilator-Induced Lung Injury

Addition of CO2 to the inspired gas can ameliorate lung injury during high tidal volume mechanical ventilation in animal models. Although some effects of hypercapnia on physiology and cell signaling have been characterized, we hypothesized that assessment of genome-wide gene expression patterns would reveal novel pathways of protection. We subjected male C57BL/6J mice to non-injurious low stretch (tidal vol = 10 mL/kg, PEEP = 2 cm H2O) or injurious high stretch (tidal volume approx 35 mL/kg, PEEP = 0 cm H2O) mechanical ventilation for 3 hours under normocapnia (FiCO2 = 0) or hypercapnia (FiCO2 = 0.12). Lung RNA was extracted from mice randomized to the following groups: non-ventilated (n = 5); low stretch normocapnia (n = 5); low stretch hypercapnia (n = 5); high stretch normocapnia (n = 10); high stretch hypercapnia (n = 10). Each RNA sample was analyzed on a separate microarray chip (no pooled samples).