Abstract
To confirm that trypsin activity is a most important initiating factor in closed duodenal loop pancreatitis in rats, we observed the course of acute pancreatitis when trypsinogen activation was inhibited by intraduodenal infusion of a potent synthetic trypsin inhibitor (TI, nafamostat mesilate) but the other conditions were left unchanged. Intraduodenal and intrapancreatic trypsinogen activation was inhibited for 16 hr after the intraduodenal infusion of the inhibitor, although elevation of serum amylase and immunoreactive trypsin and pancreatic trypsinogen remained similar both in the TI and control groups. The mortality decreased from 44% (control) to 4% (TI) at 48 hr after establishing the model. Active trypsin in duodenal reflux is an initiating factor for further development of acute pancreatitis in the closed loop model, and inhibition of the initial activation of trypsinogen has a favorable effect on acute pancreatitis even if other deleterious factors remain unchanged.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Pfeffer RB, Stasior O, Hinton JW: The clinical picture of the sequential development of acute hemorrhagic pancreatitis in the dog. Surg Forum 8:248–451, 1957
Nevalainen TJ, Seppa A: Acute pancreatitis caused by closed duodenal loop in the rats. Scand J Gastroenterol 10:521–527, 1975
Creutzfeldt W, Lankisch PG: Acute pancreatitis: Etiology and pathogenesis.In Bockus Gastroenterology, 4th ed. JE Berk (ed). Philadelphia, WB Saunders, 1985, pp 3971–3992
Aoyama T, Ino Y, Ozeki M, Oda M, Sato T, Koshiyama Y, Suzuki S, Fujita M: Pharmacological studies of FUT-175, nafamostat mesilate. I. Inhibition of protease activityin vitro andin vivo experiments. Jpn J Pharmacol 35:203–227, 1984
Caraway WT: A stable starch substrate for determination of amylase in serum and other body fluids. Am J Clin Pathol 32:97–99, 1959
Hayakawa T, Kondo T, Yamazaki Y, Mizuno R: A simple and specific determination of trypsin in human duodenal juice. Gastroenterol Jpn 15:135–139, 1980
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275, 1951
Hayakawa T, Sugimoto Y, Kondo T, Shibata T, Kitagawa M: Serum trypsin in acute experimental pancreatitis in dogs. Dig Dis Sci 31:1133, 1986
Marunaka T, Maniwa M, Matsushima E, Yoshida K, Azuma R, Kurotori M, Komatsu S: High-performance liquid Chromatographic determination of 6-amidino-2-naphthyl[4-(4, 5-dihydro-lH-imidaol-2-yl)-amino] benzoate dimethane-sulphonate and its metabolites in biological fluids. J Chromatogr 433:177–186, 1988
Takasugi S, Yonezawa H, Ikei N, Kanno T: Prevention of acute experimental pancreatitis in rats and dogs by intraduodenal infusion of a synthetic trypsin inhibitor. Digestion 24:591–598, 1982
Geokas MC, Rinderknecht H: Free proteolytic enzymes in pancreatic juice of patients with acute pancreatitis. Am J Dig Dis 19:591–598, 1974
Ohlsson K, Eddeland A: Release of proteolytic enzymes in bile-induced pancreatitis in dog. Gastroenterology 69:668–675, 1975
Wakayama T, Itoh T, Shibayama K, Idezuki Y: Prevention of the spread of experimental acute pancreatitis by intraduodenal administration of a synthetic protease inhibitor in dogs. Am J Gastroenterol 84:272–278, 1989
Hiatt N, Warner NE: Serum amylase and changes in pancreatic function and structure after ligation of pancreatic ducts. Am Surg 35:30–35, 1969
Author information
Authors and Affiliations
Additional information
Supported by a grant from the Intractable Pancreatic Disease Research Committee from the Health and Welfare Ministry of Japan.
Rights and permissions
About this article
Cite this article
Ono, H., Hayakawa, T., Kondo, T. et al. Prevention of experimental acute pancreatitis by intraduodenal trypsin inhibitor in rat. Digest Dis Sci 35, 787–792 (1990). https://doi.org/10.1007/BF01540185
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01540185