Regional effects of nafamostat, a novel potent protease and complement inhibitor, on severe necrotizing pancreatitis

Citation
T. Keck et al., Regional effects of nafamostat, a novel potent protease and complement inhibitor, on severe necrotizing pancreatitis, SURGERY, 130(2), 2001, pp. 175-181
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Surgery,"Medical Research Diagnosis & Treatment
Journal title
SURGERY
ISSN journal
0039-6060 → ACNP
Volume
130
Issue
2
Year of publication
2001
Pages
175 - 181
Database
ISI
SICI code
0039-6060(200108)130:2<175:REONAN>2.0.ZU;2-1
Abstract
Background. We evaluated the effect of the novel protease inhibitor nafamos tat on rat necrotizing pancreatitis through different routes of administrat ion. Methods. Three hours after the induction of severe pancreatitis, the rats r eceived intravenous gabexate or intravenous or local mesenteric intra-arter ial nafamostat. At 9 hours, ascites and bronchoalveolar lavage fluid were c ollected 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 lea kage in lungs (Evans blue dye, 1.6<plus/minus>0.3 vs 2.6 +/-0.3; P<.05). On ly intra-arterial infusion of nafamostat significantly diminished capillary peritoneal leakage (Evans blue dye, 3.6<plus/minus>0.9 vs 9.4 +/-0.4; P<.0 1). Typsinogen activation peptide levels were significantly reduced in all groups, but only intra-arterial infusion did so to baseline. Histologic inf lammation in the pancreas was most significantly reduced after intra-arteri al infusion (0.92<plus/minus>0.08 vs 2.91 +/-0.06; P<.05). No form of prote ase inhibition reduced mortality rates. Conclusions. The effects of protease inhibition depend on the route of admi nistration. Nafamostat has maximal effects on the pancreas and peritoneal c apillary leakage when delivered by way of local intraarterial infusion, and shows a greater reduction of lung leukocyte infiltration and capillary lea kage by the intravenous route. Nafamostat is more effective than gabexate.