Injurious Mechanical Ventilation and End-Organ Epithelial Cell Apoptosis and Organ Dysfunction in an Experimental Model of Acute Respiratory Distress Syndrome

CONTEXT Recent clinical trials have demonstrated a decrease in multiple organ dysfunction syndrome (MODS) and mortality in patients with acute respiratory distress syndrome (ARDS) treated with a protective ventilatory strategy. OBJECTIVE To examine the hypothesis that an injurious ventilatory strategy may lead to end-organ epithelial cell apoptosis and organ dysfunction. DESIGN AND SETTING In vivo animals: 24 rabbits with acid-aspiration lung injury were ventilated with injurious or noninjurious ventilatory strategies. In vitro: rabbit epithelial cells were exposed to plasma from in vivo rabbit studies. In vivo human: plasma samples from patients included in a previous randomized controlled trial examining a lung protective strategy were analyzed (lung protection group, n = 9 and controls, n = 11). MAIN OUTCOME MEASURES In vivo animals: biochemical markers of liver and renal dysfunction; apoptosis in end organs. In vitro: induction of apoptosis in LLC-RK1 renal tubular epithelial cells. In vivo human: correlation of plasma creatinine and soluble Fas ligand. RESULTS The injurious ventilatory strategy led to increased rates of epithelial cell apoptosis in the kidney (mean [SE]: injurious, 10.9% [0.88%]; noninjurious, 1.86% [0.17%]; P