title: Protective roles of hydroxyethyl starch 130/0.4 in intestinal inflammatory response and survival in rats challenged with polymicrobial sepsis.
abstract: BACKGROUND
  The gut is considered an important target organ of injury after severe insult such as sepsis, trauma and shock. Hydroxyethyl starch (HES) 130/0.4 has been developed to improve the pharmacokinetics of current medium molecular weight HES solutions. We investigated the protective effects of HES 130/0.4 on intestinal inflammatory response and survival in a rat polymicrobial sepsis model induced by cecal ligation and puncture.
  
  
  METHODS
  Animals were treated with HES 130/0.4 or saline at 4, 10, 16 or 22 h after the induction of sepsis or sham-operation and were sacrificed 2 h after resuscitation. Intestines were harvested for measurement of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-10 and macrophage inflammatory protein-2 (MIP-2) production by EELISA; intercellular adhesion molecule-1 (ICAM-1) mRNA expression by reverse-transcription PCR; nuclear factor-kappa B (NF-kappaB) by electrophoretic mobility shift assay; neutrophil sequestration by myeloperoxidase (MPO) assay; intestinal permeability by fluorescein isothiocyanate-labeled dextran assay. In addition, the role of HES 130/0.4 in rat survival was observed.
  
  
  RESULTS
  Intestinal permeability was significantly decreased after HES 130/0.4 administration in septic rats, which was associated with a reduction in inflammatory mediators and NF-kappaB activation. Furthermore, early administration of HES 130/0.4 after septic insult resulted in greater decrease in inflammatory mediators. In addition, HES 130/0.4 co-administrated with antibiotics not HES 130/0.4 alone greatly improved the survival of septic rats.
  
  
  CONCLUSIONS
  HES 130/0.4 reduced intestinal permeability by modulating inflammatory response and had a promising effect on survival together with antibiotics under septic conditions.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, P. R. China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Feng
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Sihai
authors.initials: S
authors.lastname: Zhu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism*; D007262:Infusions, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy*; D015996:Survival Rate
chemical_list: D000900:Anti-Bacterial Agents; D006895:Hydroxyethyl Starch Derivatives; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase