• Yumiko Imai, Jean Parodo, Osamu Kajikawa, Marc de Perrot, Stefan Fischer, Vern Edwards, Ernest Cutz, Mingyao Liu, Shaf Keshavjee, Thomas R Martin, John C Marshall, V Marco Ranieri, and Arthur S Slutsky.
• Department of Critical Care, St Michael's Hospital, University of Toronto, Toronto, Ontario.
• JAMA. 2003 Apr 23;289(16):2104-12.

ContextRecent 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.ObjectiveTo examine the hypothesis that an injurious ventilatory strategy may lead to end-organ epithelial cell apoptosis and organ dysfunction.Design And SettingIn 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 MeasuresIn 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.ResultsThe 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<.001) and small intestine villi (injurious, 6.7% [0.66%]; noninjurious, 0.97% [0.14%]; P<.001), and led to the elevation of biochemical markers indicating renal dysfunction in vivo. Induction of apoptosis was increased in LLC-RK1 cells incubated with plasma from rabbits ventilated with injurious ventilatory strategy at 4 hours (P =.03) and 8 hours (P =.002). The Fas:Ig, a fusion protein that blocks soluble Fas ligand, attenuated induction of apoptosis in vitro. There was a significant correlation between changes in soluble Fas ligand and changes in creatinine in patients with ARDS (R = 0.64, P =.002).ConclusionsMechanical ventilation can lead to epithelial cell apoptosis in the kidney and small intestine, accompanied by biochemical evidence of organ dysfunction. This may partially explain the high rate of MODS observed in patients with ARDS and the decrease in morbidity and mortality in patients treated with a lung protective strategy.

53 keywords...

hide…