Shock and Multiple-Organ Dysfunction after Self-Administration of Salmonella Endotoxin

Division of Pulmonary and Critical Care Medicine, Georgetown University, Washington, D.C. 20007.
New England Journal of Medicine (Impact Factor: 55.87). 06/1993; 328(20):1457-60. DOI: 10.1056/NEJM199305203282005
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    • "We decided to use a model of LPS-induced endotoxemia in rats: the systemic administration of LPS offers several advantages as it is a highly standardized and reproducible model which induces a quick and acute response [40]. Tough the administration of LPS to a human being induces the clinical manifestations of a septic shock and subsequent organ dysfunctions [41], a single injection of LPS is unlikely to mimic all facets of human sepsis. Important aspects of human sepsis are known to be better mimicked in other animal models of sepsis [42]. "
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    ABSTRACT: The use of hydroxyethyl starch (HES) in sepsis has been shown to increase mortality and acute kidney injury. However, the knowledge of the exact mechanism by which several fluids, especially starch preparations may impair end-organ function particularly in the kidney, is still missing. The aim of this study was to measure the influence of different crystalloid and colloid fluid compositions on the inflammatory response in the kidney, the liver and the lung using a rodent model of acute endotoxemia. Rats were anesthetized and mechanically ventilated. Lipopolysaccharide (5 mg/kg) was administered intravenously. After one hour crystalloids [lactate-buffered (RLac) or acetate-buffered (RAc)] were infused i.v. (30 ml/kg) in all groups. At 2 hours rats either received different crystalloids (75 ml/kg of RLac or RAc) or colloids (25 ml/kg of HES in saline or HES in RAc or gelatin in saline). Expression of messenger RNA for cytokine-induced neutrophil chemoattractant-1 (CINC-1), monocyte chemotactic protein-1 (MCP-1), necrosis factor α (TNFα) and intercellular adhesion molecule 1 (ICAM-1) was assessed in kidney, liver and lung tissue by real-time PCR after 4 hours. The use of acetate-buffered solutions was associated with a significantly higher expression of CINC-1 and TNFα mRNA in the liver, in the kidney and in the lung. Only marginal effects of gelatin and hydroxyethyl starch on mRNA expression of inflammatory mediators were observed. The study provides evidence that the type of buffering agent of different colloidal and crystalloid solutions might be a crucial factor determining the extent of early end-organ inflammatory response in sepsis.
    Full-text · Article · Apr 2014 · PLoS ONE
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    • "Endotoxin, also known as lipopolysaccharide, is a component of gram-negative bacteria and a strong activator of TLR4. The recognition of endotoxin by immune cells is important in the pathogenesis of septic shock [10] [11]. "
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    ABSTRACT: Severe sepsis results in high morbidity and mortality. Immunomodulation strategies could be an adjunctive therapy to treat sepsis. Endotoxin is a component of gram-negative bacteria and plays an important role in the pathogenesis of septic shock when it is recognized by immune cells. Removal of endotoxin could be an effective adjunctive approach to the management of sepsis. Devices to adsorb endotoxin or inflammatory cytokines have been designed as a strategy to treat severe sepsis, especially sepsis caused by gram-negative bacteria. Polymyxin B-immobilized cartridge has been successfully used to treat patients with sepsis of abdominal origin. Although this cartridge was conceived to adsorb endotoxin, several other immunological mechanisms have been elucidated, and this device has also yielded promising results in patients with nonseptic respiratory failure. In this paper, we summarize the immune modulation actions of Polymyxin B-immobilized cartridge to explore its potential usefulness beyond endotoxin elimination.
    Full-text · Article · Oct 2013 · Mediators of Inflammation
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    • "Severe inflammation can both induce coagulation and lead to disturbances of coagulation. Severe coagulation dysfunction can promote further inflammation, causing increased morbidity and mortality18,19. Among proinflammatory cytokines, TNF-α is the trigger of an inflammatory cascade and is thus crucial in local and distant organ injury; its levels also correlate well with the severity of DIC20,21. "
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    ABSTRACT: Aim: To evaluate the effects of tanshinone IIA (Tan IIA), a lipophilic diterpene from the Chinese herb Salvia miltiorrhiza, on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in rabbits. Methods: LPS-induced DIC model was made in adult male New Zealand rabbits by continuous intravenous infusion of LPS (0.5 mg/kg) via marginal ear vein for 6 h. The animals were simultaneously administered with Tan IIA (1, 3 and 10 mg/kg) or heparin (500 000 IU/kg) through continuous infusion via the contralateral marginal ear vein for 6 h. Before and 2 and 6 h after the start of LPS infusion, blood samples were taken for biochemical analyses. Results: Continuous infusion of LPS into the rabbits gradually impaired the hemostatic parameters, damaged renal and liver functions, increased the plasma TNF-α level, and led to a high mortality rate (80%). Treatment of the rabbits with Tan IIA dose-dependently attenuated the increase in activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrin-fibrinogen degradation products (FDP); ameliorated the decrease in plasma levels of fibrinogen and platelets; and reversed the decline in activity of protein C and antithrombin III. Meanwhile, the treatment significantly suppressed the increase in the plasma levels of aminotransferase, creatinine and TNF-α, and led to much lower mortality (46.7% and 26.7% for the medium- and high-dose groups). Treatment of the rabbits with the high dose of heparin also effectively improved the hemostatic parameters, ameliorated liver and renal injuries, and reduced the plasma level of TNF-α, and significantly reduced the mortality (33.3%). Conclusion: Tan IIA exerts a protective effect against DIC in rabbits.
    Full-text · Article · Sep 2012 · Acta Pharmacologica Sinica
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