Document Detail

Regional effects of nafamostat, a novel potent protease and complement inhibitor, on severe necrotizing pancreatitis.
MedLine Citation:
PMID:  11490346     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: We evaluated the effect of the novel protease inhibitor nafamostat on rat necrotizing pancreatitis through different routes of administration. METHODS: Three hours after the induction of severe pancreatitis, the rats received intravenous gabexate or intravenous or local mesenteric intra-arterial nafamostat. At 9 hours, ascites and bronchoalveolar lavage fluid were collected for the evaluation of capillary leakage (Evans blue extravasation). Pancreas and lung were excised for histologic features, myeloperoxidase, and trypsinogen activation peptide. Twenty-four hour survival was evaluated. RESULTS: Only the intravenous infusion of nafamostat significantly reduced myeloperoxidase (11.7 +/- 2.3 vs 18.3 +/- 1.8 mU/mg; P <.05) and capillary leakage in lungs (Evans blue dye, 1.6 +/- 0.3 vs 2.6 +/- 0.3; P <.05). Only intra-arterial infusion of nafamostat significantly diminished capillary peritoneal leakage (Evans blue dye, 3.6 +/- 0.9 vs 9.4 +/- 0.4; P <.01). Typsinogen activation peptide levels were significantly reduced in all groups, but only intra-arterial infusion did so to baseline. Histologic inflammation in the pancreas was most significantly reduced after intra-arterial infusion (0.92 +/- 0.08 vs 2.91 +/- 0.06; P <.05). No form of protease inhibition reduced mortality rates. CONCLUSIONS: The effects of protease inhibition depend on the route of administration. Nafamostat has maximal effects on the pancreas and peritoneal capillary leakage when delivered by way of local intra-arterial infusion, and shows a greater reduction of lung leukocyte infiltration and capillary leakage by the intravenous route. Nafamostat is more effective than gabexate.
T Keck; J H Balcom; B A Antoniu; K Lewandrowski; A L Warshaw; C F Fernández-del Castillo
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Surgery     Volume:  130     ISSN:  0039-6060     ISO Abbreviation:  Surgery     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-07     Completed Date:  2001-09-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  175-81     Citation Subset:  AIM; IM    
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, USA.
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MeSH Terms
Capillary Permeability / drug effects
Complement Inactivator Proteins / pharmacology*
Evans Blue / pharmacokinetics
Gabexate / pharmacology
Guanidines / pharmacology*
Injections, Intra-Arterial
Injections, Intravenous
Lung / enzymology
Oligopeptides / metabolism
Pancreas / pathology
Pancreatitis, Acute Necrotizing / drug therapy*,  mortality,  pathology
Peritoneum / metabolism
Peroxidase / metabolism
Protease Inhibitors / pharmacology*
Rats, Sprague-Dawley
Serine Proteinase Inhibitors / pharmacology
Survival Rate
Reg. No./Substance:
0/Complement Inactivator Proteins; 0/Guanidines; 0/Oligopeptides; 0/Protease Inhibitors; 0/Serine Proteinase Inhibitors; 0/trypsinogen activation peptide; 314-13-6/Evans Blue; 39492-01-8/Gabexate; 81525-10-2/nafamostat; EC

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

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