Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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We tested if vagus nerve stimulation (VNS) would prevent gut injury, mesenteric lymph toxicity, and systemic multiple organ dysfunction syndrome following trauma-hemorrhagic shock (T/HS). Four groups of experiments were performed. The first tested whether VNS (5 V for 10 min) would protect against T/HS-induced increases in gut and lung permeability as well as neutrophil priming. ⋯ Similar to VNS, the administration of nicotine also protected the gut from injury after T/HS. Vagus nerve stimulation prevents T/HS-induced gut injury, lung injury, neutrophil priming, and the production of biologically active mesenteric lymph. This protective effect of VNS was not dependent on the spleen but appeared to involve a cholinergic nicotinic receptor, because its beneficial effects could be replicated with nicotine.
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Gastrointestinal bacteria and epithelia contribute to systemic inflammation and infections in critically ill patients, but the gut microbiota in these diseases has not been analyzed dynamically by molecular fingerprinting methods. This study aimed to identify ileal flora dysbiosis pattern and bacterial species that changed significantly in a rat model of intestinal ischemia and reperfusion and illustrate time courses of both epithelial alterations and gut flora variations in the same injury. Forty-eight rats were randomized into eight groups (n = 6/group). ⋯ The specific dysbiosis were characterized by Escherichia coli proliferation and Lachnospiraceae and Lactobacilli reduction. These bacteria that contributed most were identified by principal component analysis and sequencing and confirmed by real-time polymerase chain reaction. In addition, alterations of ileal microbiota followed epithelial changes in the time course of reperfusion.
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Acute respiratory distress syndrome (ARDS) afflicts 200,000 patients annually with a mortality rate of 30% to 60% despite wide use of low tidal volume (LTV) ventilation, the present standard of care. High-permeability alveolar edema and instability occur early in the development of ARDS, before clinical signs of lung injury, and represent potential targets for therapy. We hypothesize that early application of a protective ventilation strategy (airway pressure release ventilation [APRV]) will stabilize alveoli and reduce alveolar edema, preventing the development of ARDS. ⋯ Protective ventilation with APRV immediately following injury prevents development of ARDS. Reduction in lung edema, preservation of lung E-cadherin, and surfactant protein A abundance in BALF suggest that APRV attenuates lung permeability, edema, and surfactant degradation. Protective ventilation could change the clinical paradigm from supportive care for ARDS with LTV ventilation to preventing development of ARDS with APRV.
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Little is known about the endothelial mechanisms involved in the anti-inflammatory effects of interleukin 10 (IL-10). The goal of this study was to evaluate the effects of IL-10 on endothelial oxidative stress and endothelial inflammation induced by tumor necrosis factor α (TNF-α). Production of reactive oxygen species (ROS) in perfused human umbilical vein endothelial cells (HUVECs) was studied by fluorescent microscopy using dichlorodihydrofluorescein diacetate. ⋯ TNF-α + IL-10: 26.8 ± 2.6 vs. 6.7 ± 0.4 adherent leukocytes/field at 15 min). Interleukin 10 decreases the level of inflammation induced by TNF-α in endothelial cells by reducing the TNF-α-induced ROS production, ICAM-1 expression, and leukocyte adhesion to the endothelium. The antioxidant effect of IL-10 is mediated through PI3-kinase and is paralleled by a decrease in ceramide synthesis induced by TNF-α.