[Show abstract][Hide abstract] 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.
PLoS ONE 04/2014; 9(4):e93863. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sepsis, a common and potentially fatal systemic illness, is triggered by microbial infection and often leads to impaired function of the lungs, kidneys or other vital organs. Since the early 1980s, a large number of therapeutic agents for the treatment of sepsis have been evaluated in randomized controlled clinical trials. With few exceptions, the results from these trials have been disappointing, and no specific therapeutic agent is currently approved for the treatment of sepsis. To improve upon this dismal record, investigators will need to identify more suitable therapeutic targets, improve their approaches for selecting candidate compounds for clinical development and adopt better designs for clinical trials.
dressNature Reviews Drug Discovery 09/2014; · 37.23 Impact Factor
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