Acute Lung Injury Caused by High Tidal Volume in a Rat Pneumonia Model

Background: To establish animal model of two-hit model for ventilator induced lung injury after pneumonia. Methods: Male Sprague-Dawley rats (300 ? 400g) were intratracheally challenged with lipopolysaccharide (LPS) as a first hit to induce lung inflammation. Rats were then randomized 24 hours later to receive mechanical ventilation as a second hit, with either an injurious strategy of high tidal volume (TV) of 22 mL/kg and zero positive end-expiratory pressure (PEEP) (high volume group, HV) or a protective strategy of low TV of 6 mL/kg with PEEP of 5 cm H2O (low volume group, LV), along with a fraction of inspired oxygen of 40 % during the experimental period. There were 4 groups (n = 8-10 rats/group): (1) HV + placebo; (2) HV + LPS; (3) LV + placebo; and (4) LV + LPS. Results: After 4-hours of ventilator use, each group had a similar hemodynamic status (mean arterial pressures and heart rates) and arterial pH, PaCO2, and HCO3 values. However, as compared with the other groups, group 2 (HV + LPS) had lower arterial O2 and lung compliance, worse lung edema, higher total and neutrophil cell counts in lung lavage fluid, and increased lung elastance and some lung cytokines. Conclusion: Inadequate ventilator settings may cause severe lung injury that is a complication after LPS induced pneumonia, as evidenced in our animal model by worse lung compliance, elastance, oxygenation, inflammatory cells, cytokines, and lung edema, which comply with evidence in the literature. Clinicians should be cautious regarding possible lung injury by inappropriate ventilator settings.