Differential effects of mechanical ventilatory strategy on lung injury and systemic organ inflammation in mice

Abstract

Patients with acute respiratory distress syndrome are at increased risk for developing multiorgan system dysfunction. The goal of this study was to establish an in vivo murine model to assess the differential effects of ventilation-protective strategies on the development of acute lung injury and systemic organ inflammation. C57B/6 mice were randomized to mechanical ventilation (MV) with conventional, high (17 ml/kg) or protective, low (6 ml/kg) tidal volume (VT) after intratracheal hydrochloric acid or no intervention. Mean arterial pressure was continuously monitored during MV and did not differ between groups. After 4 h, lung injury was assessed by measurement of wet/dry lung weight, lung lavage protein concentration and cell count, and histology. Concentration of IL-6, TNF-α, VEGF, and VEGF receptor-2 (VEGFR2) was measured in lung, liver, kidney, and heart. Results were compared with control, spontaneously breathing mice. Lung injury and altered pulmonary cytokine expression were not detected after MV of healthy mice with low or high VT. Although MV did not significantly alter IL-6 or TNF-α in systemic organs, VEGF concentration significantly increased in liver and kidney. After acid aspiration, mice ventilated with high VT manifested lung injury and increased IL-6 and VEGFR2 in lung, liver, and kidney, whereas VEGF increased only in liver and kidney. MV with low VT after acid aspiration attenuated lung injury, both IL-6 and VEGFR2 expression in lung and systemic organs, and hepatic, but not renal, increased VEGF. Our data suggest that MV strategy has differential effects on systemic inflammatory changes and thus may selectively predispose to systemic organ dysfunction.