Large Tidal Volume Ventilation Induces Lung Inflammation in an In Vivo Mouse Model

Objective To investigate the effect of prolonged period of large tidal volume [VT] ventilation on lung mechanics and inflammation. Methods After tracheostomy and arterial line placement, anesthetized mice were randomized to receive low VT (n=9), (VT 7 ml/kg, PEEP 1 cmH2O, respiratory rate [RR] 100/min, FiO2 0.5), or large VT ventilation (n=9), (VT 31 ml/kg, PEEP 0 cmH2O, RR 90/min, FiO2 0.5). Static pressure-volume [PV] curve of the respiratory system was constructed every hour. After 10 hours, arterial blood was sampled for gas analysis. Extravascular lung water [EVLW] of the right lung was calculated to assess pulmonary edema. In additional mice (n=4, each group), BAL fluid was collected after 6 hours, and total and differential cell counting was performed. Results In mice that received large VT ventilation, the PV curve progressively shifted rightward and downward, while it did not change in mice received low VT ventilation. After 10 hours of large VT vs low VT ventilation, there were no differences in PaCO2 (34±2 vs 35±3 mmHg), pH (7.31±0.02 vs 7.36±0.02), or Hb (12.4±0.3 vs 11.2±0.2 g/dl), while PaO2 was lower in the large VT group (108±19 vs 203±9 mmHg, p<0.001). The EVLW was higher after large VT ventilation than after low VT ventilation (6.4±0.6 vs 3.5±0.3 g H2O/g dry lung, p<0.001). Total cell numbers, neutrophils and lymphocytes levels were higher in BALF from mice after large VT than after low VT ventilation (total cell: 131±16 vs 88±6 x103, neutrophils: 42±18 vs 7±2x103, and lymphocytes: 5±1 vs 1±0 x103, p<0.01 for all). Conclusions In anesthetized mice, large VT ventilation recruited leukocytes to the lungs and caused pulmonary edema associated with impairment of respiratory mechanics and gas exchange. This abstract is funded by: NIH grant HL42397