Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-κB DNA binding, and improves short-term survival in lethal endotoxemia
Hemoadsorption removes tumor necrosis factor, interleukin-6, and interleukin-10, reduces nuclear factor-κB DNA binding, and improves short-term survival in lethal endotoxemia
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DOI：
10.1097/01.ccm.0000114997.39857.69
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发表时间：
2004-03-01
影响因子：
8.8
通讯作者：
Venkataraman, R
中科院分区：
文献类型：
--
作者：
Kellum, JA;Song, MC;Venkataraman, R
Objectives: Previous studies have shown that inflammatory mediators can be removed from the circulation with hemofiltration and that adsorption plays an important role. Because adsorptive capacity of hollow-fiber dialyzers is limited, we sought to determine whether hemoadsorption using high surface area beads would result in greater mediator removal and improved survival in experimental sepsis.Design: Randomized controlled laboratory experiment.Setting: University laboratory. Subjects: Sixty-six adult Sprague-Dawley rats.Interventions. We conducted two ex vivo and two in vivo experiments. For in vivo experiments, we administered Escherichia coli endotoxin (20 mg/kg) by intravenous infusion and then randomized each animal to receive either hemoadsorption or a sham circuit for 4 hrs. Hemoadsorption was performed for 4 hrs using an arterial-venous circuit and a CytoSorb cartridge containing 10 g of polystyrene divinyl benzene copolymer beads with a biocompatible polyvinylpyrrolidone coating. Survival time was measured to a maximum of 12 hrs. In a separate set of experiments, we studied 12 animals using the same protocol except that we killed all animals at 4 hrs and removed standardized sections of liver for analysis of nuclear factor-kappaB DNA binding. Measurements and Main Results, Mean survival time among hemoadsorption-treated animals was 629 +/- 114 vs. 518 +/- 120 mins for sham-treated animals (p < .01). Overall survival (defined at 12 hrs) was also significantly better in the hemoadsorption group, seven of 20 vs. one of 20 (p < .05). Plasma interleukin-6 and interleukin-10 concentrations and liver nuclear factor-kappaB DNA binding were significantly reduced by hemoadsorption. Ex vivo experiments showed no endotoxin adsorption but strengthened our in vivo observations by showing rapid adsorption of tumor necrosis factor, interleukin-6, and interieukin-10.Conclusions. Hemoadsorption was associated with reduced inflammation and improved survival in this murine model of septic shock.
