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Adverse effects of hydroxyethyl starch (HES 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with Albumin

BACKGROUND: Volume resuscitation with hydroxyethyl starch (HES) is controversially discussed and we recently showed that HES perfusion impairs endothelial and epithelial intestinal barrier integrity. Here we investigated whether Albumin containing HES solutions are superior to HES alone in maintaini...

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Autores principales: Wong, Yuk Lung, Lautenschläger, Ingmar, Zitta, Karina, Schildhauer, Christin, Parczany, Kerstin, Röcken, Christoph, Steinfath, Markus, Weiler, Norbert, Albrecht, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769564/
https://www.ncbi.nlm.nih.gov/pubmed/26920368
http://dx.doi.org/10.1186/s12967-016-0810-3
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author Wong, Yuk Lung
Lautenschläger, Ingmar
Zitta, Karina
Schildhauer, Christin
Parczany, Kerstin
Röcken, Christoph
Steinfath, Markus
Weiler, Norbert
Albrecht, Martin
author_facet Wong, Yuk Lung
Lautenschläger, Ingmar
Zitta, Karina
Schildhauer, Christin
Parczany, Kerstin
Röcken, Christoph
Steinfath, Markus
Weiler, Norbert
Albrecht, Martin
author_sort Wong, Yuk Lung
collection PubMed
description BACKGROUND: Volume resuscitation with hydroxyethyl starch (HES) is controversially discussed and we recently showed that HES perfusion impairs endothelial and epithelial intestinal barrier integrity. Here we investigated whether Albumin containing HES solutions are superior to HES alone in maintaining intestinal barrier function. METHODS: An isolated perfused model of the mouse small intestine was used to investigate the effects of: (i) 3 % Albumin (Alb), (ii) 3 % HES or (iii) 1.5 % HES/1.5 % Albumin (HES/Alb). Intestinal morphology, cell damage, metabolic functions, fluid shifts and endothelial/epithelial barrier permeability were evaluated. Potentially involved signaling mechanisms (Erk1/2, Akt and Stat5 phosphorylation) were screened. RESULTS: HES induced histomorphological damage (p < 0.01 vs. Alb), by trend elevated the amount of luminal intestinal fatty acid binding protein and reduced galactose uptake (p < 0.001 vs. Alb). Luminal and lymphatic flow rates were increased (p < 0.001 vs. Alb), while vascular flow was decreased (p < 0.001 vs. Alb) during HES perfusion. HES also increased the vascular to luminal FITC-dextran transfer (p < 0.001 vs. Alb), pointing towards a fluid shift from the vascular to the luminal and lymphatic compartments during HES perfusion. Addition of Alb (HES/Alb) reversed all adverse effects of HES (p < 0.05 vs. HES), restored barrier integrity (p < 0.05 vs. HES) and improved metabolic function of the intestine (p < 0.001 vs. HES; p < 0.05 vs. Alb). Mechanistically, HES/Alb perfusion resulted in an increased phosphorylation of Erk1/2 and Akt kinases (p < 0.001 vs. HES), while Stat5 remained unchanged. CONCLUSIONS: Albumin supplementation abrogates the adverse effects of HES in the intestine and underlying mechanism may function via phosphorylation of Erk1/2 and Akt. Albumin containing HES solutions are superior to HES alone and may improve the suitability of HES in the clinic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0810-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-47695642016-02-28 Adverse effects of hydroxyethyl starch (HES 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with Albumin Wong, Yuk Lung Lautenschläger, Ingmar Zitta, Karina Schildhauer, Christin Parczany, Kerstin Röcken, Christoph Steinfath, Markus Weiler, Norbert Albrecht, Martin J Transl Med Research BACKGROUND: Volume resuscitation with hydroxyethyl starch (HES) is controversially discussed and we recently showed that HES perfusion impairs endothelial and epithelial intestinal barrier integrity. Here we investigated whether Albumin containing HES solutions are superior to HES alone in maintaining intestinal barrier function. METHODS: An isolated perfused model of the mouse small intestine was used to investigate the effects of: (i) 3 % Albumin (Alb), (ii) 3 % HES or (iii) 1.5 % HES/1.5 % Albumin (HES/Alb). Intestinal morphology, cell damage, metabolic functions, fluid shifts and endothelial/epithelial barrier permeability were evaluated. Potentially involved signaling mechanisms (Erk1/2, Akt and Stat5 phosphorylation) were screened. RESULTS: HES induced histomorphological damage (p < 0.01 vs. Alb), by trend elevated the amount of luminal intestinal fatty acid binding protein and reduced galactose uptake (p < 0.001 vs. Alb). Luminal and lymphatic flow rates were increased (p < 0.001 vs. Alb), while vascular flow was decreased (p < 0.001 vs. Alb) during HES perfusion. HES also increased the vascular to luminal FITC-dextran transfer (p < 0.001 vs. Alb), pointing towards a fluid shift from the vascular to the luminal and lymphatic compartments during HES perfusion. Addition of Alb (HES/Alb) reversed all adverse effects of HES (p < 0.05 vs. HES), restored barrier integrity (p < 0.05 vs. HES) and improved metabolic function of the intestine (p < 0.001 vs. HES; p < 0.05 vs. Alb). Mechanistically, HES/Alb perfusion resulted in an increased phosphorylation of Erk1/2 and Akt kinases (p < 0.001 vs. HES), while Stat5 remained unchanged. CONCLUSIONS: Albumin supplementation abrogates the adverse effects of HES in the intestine and underlying mechanism may function via phosphorylation of Erk1/2 and Akt. Albumin containing HES solutions are superior to HES alone and may improve the suitability of HES in the clinic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-0810-3) contains supplementary material, which is available to authorized users. BioMed Central 2016-02-27 /pmc/articles/PMC4769564/ /pubmed/26920368 http://dx.doi.org/10.1186/s12967-016-0810-3 Text en © Wong et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wong, Yuk Lung
Lautenschläger, Ingmar
Zitta, Karina
Schildhauer, Christin
Parczany, Kerstin
Röcken, Christoph
Steinfath, Markus
Weiler, Norbert
Albrecht, Martin
Adverse effects of hydroxyethyl starch (HES 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with Albumin
title Adverse effects of hydroxyethyl starch (HES 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with Albumin
title_full Adverse effects of hydroxyethyl starch (HES 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with Albumin
title_fullStr Adverse effects of hydroxyethyl starch (HES 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with Albumin
title_full_unstemmed Adverse effects of hydroxyethyl starch (HES 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with Albumin
title_short Adverse effects of hydroxyethyl starch (HES 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with Albumin
title_sort adverse effects of hydroxyethyl starch (hes 130/0.4) on intestinal barrier integrity and metabolic function are abrogated by supplementation with albumin
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769564/
https://www.ncbi.nlm.nih.gov/pubmed/26920368
http://dx.doi.org/10.1186/s12967-016-0810-3
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