Document Detail


Sulfatide reduces leucocyte accumulation and reverts vascular failure in splanchnic artery occlusion shock.
MedLine Citation:
PMID:  9851547     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Selectin-mediated leucocyte accumulation is implicated in the pathogenesis of splanchnic artery occlusion. Sulfatide is recognized by P-selectin and blocks this adhesion molecule. We investigated the effects of sulfatide in rats subjected to splanchnic artery occlusion shock. Anaesthetized rats, subjected to total occlusion of the superior mesenteric artery and the coeliac trunk for 45 min developed severe shock resulting in death within 85-90 min after the release of occlusion. Sham operated animals were used as controls. Splanchnic artery occlusion shocked rats had marked hypotension, enhanced levels of tumor necrosis factor-alpha (TNF-alpha) in serum and macrophages, leucopenia and increased ileal leucocyte accumulation, studied by the means of myeloperoxidase activity. Furthermore, aortae from shocked rats showed marked hyporeactivity to phenylephrine (1 nM-10 microM), reduced responsiveness to acetylcholine (10 nM-10 microM) and an increased staining for P-selectin in the vasculature. In vivo administration of sulfatide (10 mg/kg, i.v., 5 min after occlusion of the splanchnic arteries) increased survival rate (90%, 4 h after splanchnic artery occlusion shock), enhanced mean arterial blood pressure, reduced serum TNF-alpha (37 +/- 11 U/ml vs. 398 +/- 18 U/ml), ameliorated leucopenia and reduced ileal myeloproxidase activity (1.2 +/- 0.4 U/g tissue vs. 8.2 +/- 0.8 U/g tissue). Aortae from splanchnic artery occlusion shocked rats treated with sulfatide exhibited a greater contractile response to phenylephrine and improved responsiveness to acetylcholine. Moreover sulfatide-treated rats showed a reduced staining for P-selectin in the aorta and in the superior mesenteric artery. Finally, passive immunization with specific monoclonal antibodies raised against P-selectin significantly protected from the lethality induced by splanchnic artery occlusion shock. Our results suggest that sulfatide protects against splanchnic artery occlusion shock.
Authors:
F Squadrito; D Altavilla; G Squadrito; G M Campo; M Arlotta; C Quartarone; L Minutoli; M Ferlito; A Saitta; A P Caputi
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  361     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1999-03-04     Completed Date:  1999-03-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  101-8     Citation Subset:  IM    
Affiliation:
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Animals
Aorta, Thoracic / drug effects,  physiopathology
Arterial Occlusive Diseases / drug therapy*
Blood Pressure / drug effects
Blood Vessels / drug effects*,  pathology
Dose-Response Relationship, Drug
Endothelium, Vascular / chemistry,  drug effects,  physiopathology
Immunohistochemistry
Leukocyte Count / drug effects
Leukocytes / cytology,  drug effects*,  metabolism,  pathology
Macrophages / cytology,  drug effects,  metabolism
Male
P-Selectin / analysis
Rats
Rats, Sprague-Dawley
Shock / drug therapy*
Splanchnic Circulation / drug effects*
Sulfoglycosphingolipids / pharmacology*
Survival Rate
Tumor Necrosis Factor-alpha / drug effects,  metabolism
Vasodilator Agents / pharmacology
Chemical
Reg. No./Substance:
0/P-Selectin; 0/Sulfoglycosphingolipids; 0/Tumor Necrosis Factor-alpha; 0/Vasodilator Agents; 51-84-3/Acetylcholine

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


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