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Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia.

Schmidt K, Hernekamp JF, Doerr M, Zivkovic AR, Brenner T, Walther A, Weigand MA, Hofer S - BMC Anesthesiol (2015)

Bottom Line: CDP-choline significantly reduced microvascular permeability in animals treated with LPS.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. karsten.schmidt@med.uni-heidelberg.de.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of CDP-choline administration on leukocyte adherence during endotoxemia. CDP-choline had no effect on the number of adhering leukocytes during endotoxemia. Scatterplots with medians are displayed. * Significant difference vs. LPS (v). Medians with interquartile range (Q1–Q3) and p values are presented in Table 2
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Fig4: Effect of CDP-choline administration on leukocyte adherence during endotoxemia. CDP-choline had no effect on the number of adhering leukocytes during endotoxemia. Scatterplots with medians are displayed. * Significant difference vs. LPS (v). Medians with interquartile range (Q1–Q3) and p values are presented in Table 2

Mentions: The experimental protocol is illustrated in Fig. 1. The color code of the experimental groups introduced in Fig. 1 is used in the results section for Fig. 2 and Fig. 4 as well.Fig. 2


Cytidine-5-diphosphocholine reduces microvascular permeability during experimental endotoxemia.

Schmidt K, Hernekamp JF, Doerr M, Zivkovic AR, Brenner T, Walther A, Weigand MA, Hofer S - BMC Anesthesiol (2015)

Effect of CDP-choline administration on leukocyte adherence during endotoxemia. CDP-choline had no effect on the number of adhering leukocytes during endotoxemia. Scatterplots with medians are displayed. * Significant difference vs. LPS (v). Medians with interquartile range (Q1–Q3) and p values are presented in Table 2
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522138&req=5

Fig4: Effect of CDP-choline administration on leukocyte adherence during endotoxemia. CDP-choline had no effect on the number of adhering leukocytes during endotoxemia. Scatterplots with medians are displayed. * Significant difference vs. LPS (v). Medians with interquartile range (Q1–Q3) and p values are presented in Table 2
Mentions: The experimental protocol is illustrated in Fig. 1. The color code of the experimental groups introduced in Fig. 1 is used in the results section for Fig. 2 and Fig. 4 as well.Fig. 2

Bottom Line: CDP-choline significantly reduced microvascular permeability in animals treated with LPS.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. karsten.schmidt@med.uni-heidelberg.de.

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.

No MeSH data available.


Related in: MedlinePlus