title: Hydroxyethyl starch (HES 130/0.4) impairs intestinal barrier integrity and metabolic function: findings from a mouse model of the isolated perfused small intestine.
abstract: BACKGROUND
  The application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine.
  
  
  METHODS
  An isolated perfused model of the mouse small intestine was established and intestines were vascularly perfused with a modified Krebs-Henseleit buffer containing 3% Albumin (N=7) or 3% HES (130/0.4; N=7). Intestinal metabolic function (galactose uptake, lactate-to-pyruvate ratio), edema formation (wet-to-dry weight ratio), morphology (histological and electron microscopical analysis), fluid shifts within the vascular, lymphatic and luminal compartments, as well as endothelial and epithelial barrier permeability (FITC-dextran translocation) were evaluated in both groups.
  
  
  RESULTS
  Compared to the Albumin group, HES perfusion did not significantly change the wet-to-dry weight ratio and lactate-to-pyruvate ratio. However, perfusing the small intestine with 3% HES resulted in a significant loss of vascular fluid (p<0.01), an increased fluid accumulation in the intestinal lumen (p<0.001), an enhanced translocation of FITC-dextran from the vascular to the luminal compartment (p<0.001) and a significantly impaired intestinal galactose uptake (p<0.001). Morphologically, these findings were associated with an aggregation of intracellular vacuoles within the intestinal epithelial cells and enlarged intercellular spaces.
  
  
  CONCLUSIONS
  A vascular perfusion with 3% HES impairs the endothelial and epithelial barrier integrity as well as metabolic function of the small intestine.
authors: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany; Division of Barrier Integrity, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
authors: Yuk Lung
authors: YL
authors: Wong
authors: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany; Division of Barrier Integrity, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
authors: Ingmar
authors: I
authors: Lautenschläger
authors: Division of Barrier Integrity, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
authors: Heike
authors: H
authors: Dombrowsky
authors: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors: Karina
authors: K
authors: Zitta
authors: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors: Berthold
authors: B
authors: Bein
authors: Division of Mucosal Immunology and Diagnostics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
authors: Thorsten
authors: T
authors: Krause
authors: Division of Clinical and Experimental Pathology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
authors: Torsten
authors: T
authors: Goldmann
authors: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors: Inez
authors: I
authors: Frerichs
authors: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors: Markus
authors: M
authors: Steinfath
authors: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors: Norbert
authors: N
authors: Weiler
authors: Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors: Martin
authors: M
authors: Albrecht
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010477:Perfusion; D010539:Permeability / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D019344:Lactic Acid; D019289:Pyruvic Acid