Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia
BACKGROUND: Microvascular permeability and leukocyte adhesion are pivotal mechanisms in sepsis pathophysiology contributing to the development of shock and mortality. No effective pharmacological therapy is currently available to restore microvascular barrier function in sepsis. Cholinergic mediator...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522138/ https://www.ncbi.nlm.nih.gov/pubmed/26232247 http://dx.doi.org/10.1186/s12871-015-0086-9 |
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author | Schmidt, Karsten Hernekamp, Jochen Frederick Doerr, Miriam Zivkovic, Aleksandar R. Brenner, Thorsten Walther, Andreas Weigand, Markus A. Hofer, Stefan |
author_facet | Schmidt, Karsten Hernekamp, Jochen Frederick Doerr, Miriam Zivkovic, Aleksandar R. Brenner, Thorsten Walther, Andreas Weigand, Markus A. Hofer, Stefan |
author_sort | Schmidt, Karsten |
collection | PubMed |
description | BACKGROUND: Microvascular permeability and leukocyte adhesion are pivotal mechanisms in sepsis pathophysiology contributing to the development of shock and mortality. No effective pharmacological therapy is currently available to restore microvascular barrier function in sepsis. Cholinergic mediators have been demonstrated to exert anti-inflammatory effects during inflammation. Cytidine-5-diphosphocholine (CDP-choline) is an extensively studied cholinergic drug due to its brain protective characteristics in cerebrovascular diseases. This study evaluated the effect of CDP-choline on microvascular permeability and leukocyte adhesion during endotoxemia. METHODS: Macromolecular leakage, leukocyte adhesion, and venular wall shear rate were examined in mesenteric postcapillary venules of rats by using intravital microscopy (IVM). Lipopolysaccharide (LPS) (4 mg/kg/h) or equivalent volumes of saline were continuously infused following baseline IVM at 0 min. IVM was repeated after 60 and 120 min in endotoxemic and nonendotoxemic animals. CDP-choline (100 mg/kg) was applied as an i.v. bolus. Animals received either saline alone, CDP-choline alone, CDP-choline 10 min before or 30 min after LPS administration, or LPS alone. Due to nonparametric data distribution, Wilcoxon test and Dunn's multiple comparisons test were used for data analysis. Data were considered statistically significant at p < 0.05. RESULTS: Treatment with LPS alone significantly increased microvascular permeability and leukocyte adhesion and decreased venular wall shear rate. CDP-choline significantly reduced microvascular permeability in animals treated with LPS. Leukocyte adhesion and venular wall shear rate were not affected by CDP-choline during endotoxemia. CONCLUSION: CDP-choline has a protective effect on microvascular barrier function during endotoxemia. Considering the excellent pharmacologic safety profile of CDP-choline, its use could be an approach for the treatment of capillary leakage in sepsis. |
format | Online Article Text |
id | pubmed-4522138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45221382015-08-02 Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia Schmidt, Karsten Hernekamp, Jochen Frederick Doerr, Miriam Zivkovic, Aleksandar R. Brenner, Thorsten Walther, Andreas Weigand, Markus A. Hofer, Stefan BMC Anesthesiol Research Article BACKGROUND: Microvascular permeability and leukocyte adhesion are pivotal mechanisms in sepsis pathophysiology contributing to the development of shock and mortality. No effective pharmacological therapy is currently available to restore microvascular barrier function in sepsis. Cholinergic mediators have been demonstrated to exert anti-inflammatory effects during inflammation. Cytidine-5-diphosphocholine (CDP-choline) is an extensively studied cholinergic drug due to its brain protective characteristics in cerebrovascular diseases. This study evaluated the effect of CDP-choline on microvascular permeability and leukocyte adhesion during endotoxemia. METHODS: Macromolecular leakage, leukocyte adhesion, and venular wall shear rate were examined in mesenteric postcapillary venules of rats by using intravital microscopy (IVM). Lipopolysaccharide (LPS) (4 mg/kg/h) or equivalent volumes of saline were continuously infused following baseline IVM at 0 min. IVM was repeated after 60 and 120 min in endotoxemic and nonendotoxemic animals. CDP-choline (100 mg/kg) was applied as an i.v. bolus. Animals received either saline alone, CDP-choline alone, CDP-choline 10 min before or 30 min after LPS administration, or LPS alone. Due to nonparametric data distribution, Wilcoxon test and Dunn's multiple comparisons test were used for data analysis. Data were considered statistically significant at p < 0.05. RESULTS: Treatment with LPS alone significantly increased microvascular permeability and leukocyte adhesion and decreased venular wall shear rate. CDP-choline significantly reduced microvascular permeability in animals treated with LPS. Leukocyte adhesion and venular wall shear rate were not affected by CDP-choline during endotoxemia. CONCLUSION: CDP-choline has a protective effect on microvascular barrier function during endotoxemia. Considering the excellent pharmacologic safety profile of CDP-choline, its use could be an approach for the treatment of capillary leakage in sepsis. BioMed Central 2015-08-01 /pmc/articles/PMC4522138/ /pubmed/26232247 http://dx.doi.org/10.1186/s12871-015-0086-9 Text en © Schmidt et al. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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 Article Schmidt, Karsten Hernekamp, Jochen Frederick Doerr, Miriam Zivkovic, Aleksandar R. Brenner, Thorsten Walther, Andreas Weigand, Markus A. Hofer, Stefan Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia |
title | Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia |
title_full | Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia |
title_fullStr | Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia |
title_full_unstemmed | Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia |
title_short | Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia |
title_sort | cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522138/ https://www.ncbi.nlm.nih.gov/pubmed/26232247 http://dx.doi.org/10.1186/s12871-015-0086-9 |
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