脂肪酸在急重症的应用.pptxVIP

N-3 Lipids in Critical Care MedicineDr. Konstantin MayerUniversity of Giessen Lung CenterPulmonary and Critical Care MedicineUniversity Hospital Giessen and MarburgLipid Mediator SynthesisImpact of n-3 vs. n-6 Fatty Acids on InflammationN-3 Lipidsvasomotor dysfunctionO2 pulmonary hypertension VQ-mismatch / ShuntO2QO2 leukocyte invasion vascular leakageCapillary sequestrationAlveolar invasiongas exchange ?secundary bacterial invasionKey Features of Acute Lung Injury Randomized, controlled study21 Pts with septic ARDS LCT or LCT/MCT @ 12g/hPulmonary hemodynamics / Ventilation parameterResultsLCT (n-6)Increase in Pulmonary Artery Pressure (MPAP) Decrease in Oxygenation-Index (PaO2 / FiO2)Grimminger, Mayer et al. J Pharm Exp Ther 1993, Am J Physiol 1995Protective impact of n-3 fatty acidson edema-formation in a model of septic lung failureLTB4 ++++LTB4 ++LTB4 +LTB5 ++++Am J Resp Cell Mol Biol 1997Am J Resp Crit Care Med 1997, Am J Physiol 2000Effects of Parenteral Application ofFish Oil versus Soy Bean Oil Emulsionson Bacterial Clearance FunctionsI. Kelbel, T. Koch, A. Prechtl, A. Heller,E. Schlotzer, H.G. Schiefer, H. Neuhof Infusion Therapy & Transfusion Medicine: 26, 226-232, 1999Experimental Protocol(Kelbel et al., 1999)Design: 36 rabbits, randomly assigned to 6 groupsTreatment: 1.5 g/kg b.w./day for 3 days of a - fish oil emulsion (n-3 rich) - a soybean oil emulsion (n-6 rich) or - 0.9% saline (Control) E. coli intravenous injection (1.3 x 108 CFU) Sacrifice of animals 3 or 6 h after bact. injectionParameters: Bacterial counts in lung, liver, spleen & kidney Number of bacterial colonies in the lungKelbel et al. 1999Long-term lipid-infusion in miceLeukocyte Invasion in a Model of Acute Lung Injury – Impact of n-3 Lipids*BALBroncho alveolar lavageLPSlipopolysaccharideLPSCrit Care Med 2007Enteral n-3 lipids + anti-oxidants:N-3 Lipids & ARDSRCT of 146 critically ill patients acute lung injury and positive bronchoalveolar lavage for leukocytesDouble-blindedE