MV of acid-injured lungs resulted in greater physiologic and histological indices of lung injury compared to control groups. Additionally, there was an immediate and significant release of multiple inflammatory mediators from the lung into the systemic circulation which resulted in greater levels of mRNA adhesion molecule expression in liver endothelial cells in vitro. Conclusions: This study suggests that MV, specifically tidal volume strategy, influences the development of MOF through an

more »

... ulation of lung-derived systemic inflammation resulting in maladaptive cellular changes in peripheral organs. Introduction Acute lung injury (ALI) and its more severe formacute respiratory distress syndrome (ARDS) -represent a spectrum of pulmonary disorders characterized by hypoxemia and reduced lung compliance, in the absence of left-sided heart failure. Despite optimal supportive care of these critically ill patients, mortality due to ALI remains exceedingly high, at approximately 30-40% [1] , with multiple organ failure (MOF) representing the most common cause of death [2, 3] . The mechanisms leading to the development of non-pulmonary organ failure in this setting remain largely uncharacterized. Abstract Background: Overwhelming systemic inflammation has been implicated in the progression of acute lung injury (ALI) leading to multiple organ failure (MOF) and death. Previous studies suggest that mechanical ventilation (MV) may be a key mediator of MOF through an upregulation of the systemic inflammatory response. Objectives: It was the aim of this study to investigate mechanisms whereby mechanical stress induced by different tidal volumes may contribute to the development of systemic inflammation and maladaptive peripheral organ responses in the setting of ALI. Methods: An acid aspiration model of ALI was employed in 129X1/SVJ mice through an intratracheal administration of hydrochloric acid followed by MV employing either a low (5 ml/kg) or high (12.5 ml/kg) tidal volume ventilation for 120 min. The isolated perfused mouse lung setup was used to assess the specific contribution of the lung to systemic inflammation during MV. Furthermore, lung perfusate collected over the course of MV was used to assess the effects of lung-derived mediators on activation (expression of a proadhesive phenotype) of liver endothelial cells. Results: High tidal volume