Experimental TLR4 inhibition improves intestinal microcirculation in endotoxemic rats Juan Zhou, Marieke Soltow, Katrin Zimmermann, Dragan Pavlovic, Brent Johnston, Christian Lehmann PII: DOI: Reference:
S0026-2862(15)30001-7 doi: 10.1016/j.mvr.2015.06.004 YMVRE 3546
To appear in:
Microvascular Research
Accepted date:
22 June 2015
Please cite this article as: Zhou, Juan, Soltow, Marieke, Zimmermann, Katrin, Pavlovic, Dragan, Johnston, Brent, Lehmann, Christian, Experimental TLR4 inhibition improves intestinal microcirculation in endotoxemic rats, Microvascular Research (2015), doi: 10.1016/j.mvr.2015.06.004
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ACCEPTED MANUSCRIPT Experimental TLR4 inhibition improves intestinal microcirculation in endotoxemic rats
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Juan Zhou1,2, Marieke Soltow3, Katrin Zimmermann3, Dragan Pavlovic3, Brent Johnston2 and Christian Lehmann1,2 Departments of Anesthesia and 2Microbiology & Immunology, Dalhousie University, 5850 College St., Halifax, B3H 4R2, Nova Scotia, Canada
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Christian Lehmann Dalhousie University 5850 College Street 6H Tupper Building Halifax, NS, B3H 1X5 Canada E-mail:
[email protected]
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Corresponding author:
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Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-University, Loefflerstr. 23, 17475 Greifswald, Germany
ACCEPTED MANUSCRIPT Abstract
Introduction: Toll like receptor 4 (TLR4) represents a critical cellular link for endotoxin-induced pathology. The aim of this study was to evaluate the potential role of TLR4 inhibition on the intestinal
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microcirculation during experimental endotoxemia.
Materials and Methods: The intestinal microcirculation was studied by intravital microscopy in four
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groups of Lewis rats (n=10 per group): healthy controls (CON group), endotoxemic animals (15 mg/kg lipopolysaccharide, LPS group), endotoxemic animals treated with a TLR4 antagonist (1 mg/kg CRX-
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526, LPS+CRX group), and controls treated with CRX-526 (CRX group). Plasma samples were
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obtained for cytokine measurements at the end of the experiments.
Results: Endotoxemia significantly increased leukocyte adhesion in intestinal submucosal venules (e.g., V1 venules: CON 20.4±6.5 n/mm2, LPS 237.5±36.2 n/mm2, p
