Source:http://linkedlifedata.com/resource/pubmed/id/18670364
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2008-8-21
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| pubmed:abstractText |
Animal data strongly support a role for inflammation in myocardial ischemia reperfusion injury. Attempts at cardioprotection by immunomodulation (such as with the specific C5 antibody pexelizumab) in humans have been disappointing. We hypothesized that a broader spectrum antiinflammatory agent might yield successful cardioprotection. The serine protease inhibitor nafamostat (FUT-175), which is already in clinical use, is a potent antiinflammatory synthetic serine protease inhibitor with anticomplement activity that we tested in a well-established rabbit model of 1 hour of myocardial ischemia followed by 3 hours of reperfusion. Compared to vehicle-treated animals, nafamostat (1 mg/kg of body weight) administered 5 minutes before reperfusion significantly reduced myocardial injury assessed by plasma creatine kinase activity (38.1 +/- 6.0 versus 57.9 +/- 3.7I U/g protein; P < 0.05) and myocardial necrosis (23.6 +/- 3.1% versus 35.7 +/- 1.0%; P < 0.05) as well as myocardial leukocyte accumulation (P < 0.05). In parallel in vitro studies, Nafamostat was a significantly more potent broad spectrum complement suppressor than C1 inhibitor. Nafamostat appears to have capability as an inhibitor of both complement pathways and as a broad-spectrum antiinflammatory agent by virtue of its serine protease inhibition. Administration of nafamostat before myocardial reperfusion after ischemia produced significant, dose-dependent cardioprotection. Reduced leukocyte accumulation and complement activity seem involved in the mechanism of this cardioprotective effect.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C1 Inhibitor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Complement Inactivating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Creatine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Guanidines,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/nafamostat
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1533-4023
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
52
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
151-60
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| pubmed:meshHeading |
pubmed-meshheading:18670364-Animals,
pubmed-meshheading:18670364-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:18670364-Complement Activation,
pubmed-meshheading:18670364-Complement C1 Inhibitor Protein,
pubmed-meshheading:18670364-Complement Inactivating Agents,
pubmed-meshheading:18670364-Complement Pathway, Alternative,
pubmed-meshheading:18670364-Complement Pathway, Classical,
pubmed-meshheading:18670364-Creatine Kinase,
pubmed-meshheading:18670364-Guanidines,
pubmed-meshheading:18670364-Hemodynamics,
pubmed-meshheading:18670364-Humans,
pubmed-meshheading:18670364-Immunohistochemistry,
pubmed-meshheading:18670364-Male,
pubmed-meshheading:18670364-Myocardial Reperfusion Injury,
pubmed-meshheading:18670364-Myocardium,
pubmed-meshheading:18670364-Necrosis,
pubmed-meshheading:18670364-Neutrophils,
pubmed-meshheading:18670364-Rabbits,
pubmed-meshheading:18670364-Serine Proteinase Inhibitors
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| pubmed:year |
2008
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| pubmed:articleTitle |
Serine protease inhibitor nafamostat given before reperfusion reduces inflammatory myocardial injury by complement and neutrophil inhibition.
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| pubmed:affiliation |
Department of Medicine III, Martin-Luther-University, Halle, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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