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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6 Pt 1
pubmed:dateCreated
1998-2-9
pubmed:abstractText
Adhesion of leukocytes to the vascular endothelium hallmarks a key event in neutrophil-mediated organ injury after ischemia-reperfusion. The autacoid adenosine has been shown to inhibit activated neutrophil function and to interfere with leukocyte-endothelial adherence. Its therapeutic use in ischemia-reperfusion, however, has been limited by severe cardiovascular side effects. We therefore investigated the effects of the adenosine kinase inhibitor GP515 in vivo on hepatic leukocyte-endothelial interactions in a rat model of hemorrhagic hypotension and resuscitation, using intravital microscopy. Rats were pretreated with either GP515 (0.25 mg/kg) or saline in a randomized and blinded manner and subjected to pressure-controlled hemorrhagic hypotension at a mean arterial pressure of 40 mmHg for 60 min followed by 5 h of resuscitation. Five hours after resuscitation in saline-treated animals, firm leukocyte-sinusoidal adhesion was strongly enhanced in the periportal and midzonal sublobular regions, and sinusoidal diameters were also markedly reduced. Compared with saline treatment, GP515 significantly attenuated shock and resuscitation-induced leukocyte adhesion in both sublobular regions. Moreover, although GP515 did not significantly affect macrohemodynamical and hematological parameters, it enlarged narrowed sinusoidal diameters and tended to improve sinusoidal blood flow. We propose that the adenosine-regulating agent GP515 has a therapeutic potential to attenuate ischemia-reperfusion-induced inflammation by capitalizing on the beneficial anti-inflammatory effects of endogenous adenosine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G1297-303
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9435554-Adenosine Kinase, pubmed-meshheading:9435554-Animals, pubmed-meshheading:9435554-Blood Pressure, pubmed-meshheading:9435554-Carbon Dioxide, pubmed-meshheading:9435554-Cardiac Output, pubmed-meshheading:9435554-Cell Adhesion, pubmed-meshheading:9435554-Enzyme Inhibitors, pubmed-meshheading:9435554-Female, pubmed-meshheading:9435554-Heart Rate, pubmed-meshheading:9435554-Hemodynamics, pubmed-meshheading:9435554-Hemoglobins, pubmed-meshheading:9435554-Hypotension, pubmed-meshheading:9435554-Leukocyte Count, pubmed-meshheading:9435554-Leukocytes, pubmed-meshheading:9435554-Oxygen, pubmed-meshheading:9435554-Partial Pressure, pubmed-meshheading:9435554-Rats, pubmed-meshheading:9435554-Rats, Sprague-Dawley, pubmed-meshheading:9435554-Resuscitation, pubmed-meshheading:9435554-Ribonucleosides, pubmed-meshheading:9435554-Shock, Hemorrhagic
pubmed:year
1997
pubmed:articleTitle
Adenosine kinase inhibitor GP515 attenuates hepatic leukocyte adhesion after hemorrhagic hypotension.
pubmed:affiliation
Department of Anesthesiology, University of Saarland, Homburg/Saar, Germany.
pubmed:publicationType
Journal Article