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Activated protein C improves pial microcirculation in experimental endotoxemia in rats.

Authors: Zhou, J  Pavlovic, D  Willecke, J  Friedel, C  Whynot, S  Hung, O  Cerny, V  Schroeder, H  Wendt, M  Shukla, R  Lehmann, C 
Citation: Zhou J, etal., Microvasc Res. 2012 May;83(3):276-80. doi: 10.1016/j.mvr.2012.03.003. Epub 2012 Mar 9.
Pubmed: (View Article at PubMed) PMID:22426124
DOI: Full-text: DOI:10.1016/j.mvr.2012.03.003

INTRODUCTION: The brain is one of the first organs affected clinically in sepsis. Microcirculatory alterations are suggested to be a critical component in the pathophysiology of sepsis. The aim of this study was to investigate the effects of recombinant human activated protein C (rhAPC) on the pial microcirculation in experimental endotoxemia using intravital microscopy. Our hypothesis is rhAPC protects pial microcirculation in endotoxemia. METHODS: Endotoxemia was generated in Lewis rats with intravenous injection of lipopolysaccharide (LPS, 5 mg/kg i.v.). Dura mater was removed through a cranial window to expose pial vessels on the brain surface. The microcirculation, including leukocyte-endothelial interaction, functional capillary density (FCD) and plasma extravasation of pial vessels was examined by fluorescent intravital microscopy (IVM) 2 h after administration of LPS, LPS and rhAPC or equivalent amount of saline (used as Control group). Plasma cytokine levels of interleukin 1 alpha (IL1-alpha), tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), Monocyte chemotactic protein-1 (MCP-1) and Granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated after IVM. RESULTS: LPS challenge significantly increased leukocyte adhesion (773+/-190 vs. 592+/-152 n/mm(2) Control), decreased FCD (218+/-54 vs. 418+/-74 cm/cm(2) Control) and increased proinflammatory cytokine levels (IL-1alpha: 5032+/-1502 vs. 8+/-21 pg/ml; TNF-alpha: 1823+/-1007 vs. 168+/-228 pg/ml; IFN-gamma: 785+/-434 vs. 0 pg/ml; GM-CSF: 54+/-52 vs. 1+/-3 pg/ml) compared to control animals. rhAPC treatment significantly reduced leukocyte adhesion (599+/-111 n/mm(2)), increased FCD (516+/-118 cm/cm(2)) and reduced IL-1alpha levels (2134+/-937 pg/ml) in the endotoxemic rats. CONCLUSION: APC treatment significantly improves pial microcirculation by reducing leukocyte adhesion and increasing FCD.


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RGD Object Information
RGD ID: 7794786
Created: 2014-01-10
Species: All species
Last Modified: 2014-01-10
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.