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Effects of hydroxyethyl starch 130/0.4 on pulmonary capillary leakage and cytokines production and NF-kappaB activation in CLP-induced sepsis in rats.

Feng X, Yan W, Liu X, Duan M, Zhang X, Xu J

Department of Anesthesiology Jinling Hospital, School of Medicine, Nanjing University, Nanjing, P. R. China.

BACKGROUND: Sepsis and resulting multiple system organ failure are the leading causes of mortality in intensive care units. Hydroxyethyl starch (HES) 130/0.4 was a novel preparation, developed to improve the pharmacokinetics of current medium molecular weight HES solutions. This study was designed to explore the effects of HES 130/0.4 on pulmonary capillary permeability (PCP), production of cytokines, and activation of transcription factor in septic rats induced by cecal ligation and puncture (CLP). MATERIALS AND METHODS: Adult male Sprague Dawley rats were randomly divided into six groups (six rats/group): saline controls (30 ml/kg); CLP plus saline (30 ml/kg); CLP plus HES (7.5, 15, or 30 ml/kg, respectively), and HES alone (30 ml/kg). Mean arterial blood pressure and heart rate were monitored during the experiment process. Myeloperoxidase (MPO) activity, wet/dry weight ratio, PCP, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, IL-10, and nuclear factor-kappa B (NF-kappaB) were investigated at 6 h. RESULTS: We demonstrated that CLP could provoke significant injury in lung, characterized by increase in PCP, wet/dry weight ratio, MPO activity, TNF-alpha, IL-6, and IL-10 level, and NF-kappaB activation. Without obvious influence on systemic macro-hemodynamics, HES 15 ml/kg and 30 ml/kg significantly reduced CLP-induced elevation of pulmonary capillary permeability, wet/dry weight ratio, and production of IL-6. Meanwhile, HES 15 ml/kg increased IL-10 level and HES 7.5, 15, and 30 ml/kg suppressed MPO activity, TNF-alpha level, and NF-kappaB activation. CONCLUSION: HES 130/0.4 can inhibit CLP-induced PCP by attenuating pulmonary inflammation and NF-kappaB activation in vivo.

Published 21 August 2006 in J Surg Res, 135(1): 129-36.
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