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...

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Autores principales: Schmidt, Karsten, Hernekamp, Jochen Frederick, Doerr, Miriam, Zivkovic, Aleksandar R., Brenner, Thorsten, Walther, Andreas, Weigand, Markus A., Hofer, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
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.
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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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