%0 Journal Article %A Yung-Yang Liu %A Chi-Huei Chiang %A Chiao-Hui Chuang %A Shiou-Ling Liu %A Yi-Han Jheng %A Jay H Ryu %T Spillover of Cytokines and Reactive Oxygen Species in Ventilator-Induced Lung Injury Associated With Inflammation and Apoptosis in Distal Organs %D 2014 %R 10.4187/respcare.02992 %J Respiratory Care %P 1422-1432 %V 59 %N 9 %X BACKGROUND: The mechanism between ventilator-induced lung injury (VILI) and multiple organ injury is unclear. The aim of our study was to investigate the mechanisms of VILI-induced distal organ injury. METHODS: VILI was induced in rat lungs with high tidal volume (VT) ventilation of 40 mL/kg for 6 h. Rats with low VT ventilation of 6 mL/kg served as controls. Inflammatory and apoptotic indices in lung and distal organs were assessed. RESULTS: VILI increased lung weight, airway pressure, inflammation, and apoptotic pathologic changes without hemodynamic changes. The white blood cell count and the levels of H2O2, interleukin-1β (IL-1β), tumor necrosis factor alpha, and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid were higher in the VILI group compared with the control group. H2O2, IL-1β, and tumor necrosis factor alpha in blood from the left ventricle were up-regulated. H2O2, IL-1β, tumor necrosis factor alpha, macrophage inflammatory protein-2, c-Jun N-terminal kinase, p38, nuclear factor kappa B, and caspase-3 in lung, heart, liver, and kidney tissues in the VILI group were up-regulated. Furthermore, the apoptotic score for the kidneys was higher than those for other distal organs in the VILI group. CONCLUSIONS: High VT ventilation induces VILI and is associated with inflammation and apoptosis in distal organs. Up-regulation of reactive oxygen species and cytokines in VILI is associated with systemic inflammatory responses. Kidney tissue appears to be more vulnerable than heart and liver tissues following VILI. %U https://rc.rcjournal.com/content/respcare/59/9/1422.full.pdf