Document Detail

Effect of WEB 2086 on leukocyte adherence in response to hemorrhagic shock in rats.
MedLine Citation:
PMID:  11130496     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The pathogenesis of generalized microvascular injury after hemorrhagic shock is known to involve the generation of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine [PAF]). The release of PAF is manifested in several ways, including by increased vascular permeability, altered vascular reactivity, and increased leukocyte adherence to the endothelium. WEB 2086 is a PAF antagonist that has been shown experimentally to improve survival after hemorrhagic shock. The purpose of this study was to examine the efficacy of WEB 2086 in attenuating leukocyte adherence before, during, and after hemorrhagic shock. METHODS: After a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 minutes in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of the small bowel were examined to quantitate leukocyte adherence using intravital microscopy. RESULTS: In sham-operated rats (control), there was minimal to no leukocyte adherence throughout the experiment. Hemorrhagic shock resulted in a significant increase in leukocyte adherence postshock during resuscitation (10.9 +/- 1.8 cells/100 microm, p < 0.01) when compared with controls. WEB 2086, when given before shock, significantly attenuated leukocyte adherence (0.1 +/- 0.08 cells/100 microm, p < 0.01) when compared with hemorrhagic shock alone. This effect of WEB 2086 on adherence could be demonstrated even when it was given during (3.5 +/- 0.9 cells/100 microm, p < 0.01) and 10 minutes into (5.8 +/- 1.1 cells/100 microm, p < 0.05) hemorrhagic shock. CONCLUSION: Our findings suggest that WEB 2086 may be of therapeutic benefit against the microvascular damage sustained after hemorrhagic shock.
E W Childs; D M Smalley; M Moncure; J L Miller; L Y Cheung
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of trauma     Volume:  49     ISSN:  0022-5282     ISO Abbreviation:  J Trauma     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2000-12-20     Completed Date:  2001-01-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376373     Medline TA:  J Trauma     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1102-7     Citation Subset:  AIM; IM    
Department of Surgery, University of Kansas Medical Center, Kansas City 66160, USA.
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MeSH Terms
Azepines / pharmacology*
Cell Adhesion / drug effects
Disease Models, Animal
Leukocytes / drug effects*
Platelet Aggregation Inhibitors / pharmacology*
Rats, Sprague-Dawley
Shock, Hemorrhagic / physiopathology*
Triazoles / pharmacology*
Grant Support
Reg. No./Substance:
0/Azepines; 0/Platelet Aggregation Inhibitors; 0/Triazoles; 105219-56-5/WEB 2086

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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