eprintid: 19444
rev_number: 16
eprint_status: archive
userid: 1589
dir: disk0/00/01/94/44
datestamp: 2016-01-12 14:04:55
lastmod: 2024-04-17 00:54:19
status_changed: 2016-01-12 14:04:55
type: article
metadata_visibility: show
creators_name: Schmidt, Karsten
creators_name: Hernekamp, Jochen Frederick
creators_name: Dörr, Miriam
creators_name: Zivkovic, Aleksandar R.
creators_name: Brenner, Thorsten
creators_name: Walther, Andreas
creators_name: Weigand, Markus A.
creators_name: Hofer, Stefan
title: Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia
subjects: ddc-610
divisions: i-910200
divisions: i-910300
abstract: 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.  
date: 2015
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 1653717750
own_urn: urn:nbn:de:bsz:16-heidok-194448
language: eng
bibsort: SCHMIDTKARCYTIDINE5D2015
full_text_status: public
publication: BMC anesthesiology
volume: 15
number: 114
place_of_pub: London
pagerange: 1-9
issn: 1471-2253
citation:   Schmidt, Karsten ; Hernekamp, Jochen Frederick ; Dörr, Miriam ; Zivkovic, Aleksandar R. ; Brenner, Thorsten ; Walther, Andreas ; Weigand, Markus A. ; Hofer, Stefan  (2015) Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia.  BMC anesthesiology, 15 (114).  pp. 1-9.  ISSN 1471-2253     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19444/1/12871_2015_Article_86.pdf