Abstract
In the present study we investigated the therapeutic action of antithrombin III (AT III) in taurocholate-induced experimental pancreatitis with high lethality in rats. High-dose AT III treatment greatly improved the survival rate not only when given as pretreatment but also when given 2 hr after induction. No favorable effect on survival rate was observed on administration after 5 hr. Both intravascular and intraperitoneal AT III administration locally restored decreased AT III levels in the peritoneal cavity and increased plasma AT III to supranormal levels. The primary pancreatic insult seemed to be unaffected by the treatment, because neither the rise in plasma lipase nor the development of ascites or the extension of the pancreatic necrosis were diminished. Because heparin pretreatment of the rats was also effective, the mechanism of the beneficial action was probably mediated by inhibition of the proteases of the coagulation cascade, thereby preventing intravascular coagulation in the pancreas and distant organs and subsequent systemic complications. The high efficacy of AT III treatment in this experimental model may stimulate clinical studies evaluating the efficacy of AT III treatment in an early stage of acute pancreatitis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Geokas MC, Baltaxe HA, Banks PA, Silva J, Frey CF: Acute pancreatitis. Ann Intern Med 103:86–100, 1985
Pitchumoni CS, Agarwal N, Jain NK: Systemic complications of acute pancreatitis. Am J Gastroenterol 83:597–606, 1988
Lasson A, Ohlsson K: Acute pancreatitis. The correlation between clinical course, protease inhibitors, and complement and kinin activation. Scand J Gastroenterol 19:707–710, 1984
Dubick MA, Mayer AD, Majumdar APN, Mar G, McMahon MJ, Geokas MC: Biochemical studies in peritoneal fluid from patients with acute pancreatitis. Relationship to etiology. Dig Dis Sci 32:305–312, 1987
McMahon MJ, Bowen M, Mayer AD, Cooper EH: Relation of alpha2-macroglobulin and other antiproteases to the clinical features of acute pancreatitis. Am J Surg 147:164–170, 1984
Goodman AJ, Bird NC, Johnson AG: Antiprotease capacity in acute pancreatitis. Br J Surg 73:796–798, 1986
Lasson A, Ohlsson K: Consumptive coagulopathy, fibrinolysis and protease-antiprotease interactions during acute human pancreatitis. Thromb Res 41:167–183, 1986
Steinberg WM, Schlesselman SE. Treatment of acute pancreatitis. Comparison of animal and human studies. Gastroenterology 93:1420–1427, 1987
Niederau C, Crass RA, Silver G, Ferrell LD, Grendell JH: Therapeutic regimens in acute experimental hemorrhagic pancreatitis: Effects of hydration, oxygenation, peritoneal lavage, and a potent protease inhibitor. Gastroenterology 95:1648–1657, 1988
Lankisch PG, Pohl U, Göke B, Otto J, Wereszczynska-Siemiatkowska U, Gröne H-J, Rahlf G: Effect of FOY-305 (camostate) on severe acute pancreatitis in two experimental animal models. Gastroenterology 96:193–199, 1989
Ruud TE, Aasen AO, Pillgram-Larsen J, Stadaas JO: Effects on peritoneal proteolysis and hemodynamics of prophylactic infusion with C1 inhibitor in experimental acute pancreatitis. Scand J Gastroenterol 21:1018–1024, 1986
Heinkel K: Die ratte als versuchstier in der experimentellen pankreas-diagnostiek. Die erzeugung einer akuten hamorrhagischen pankreatitis durch injektion von gallensaure in den ductus pancreaticus. Klin Wochenschr 31:815–815, 1953
Aho HJ, Koskensalo SML, Nevalainen TJ: Experimental pancreatitis in the rat. Sodium taurocholate-induced acute hemorrhagic pancreatitis. Scand J Gastroenterol 15:411–416, 1980
Kabat EA, Mayer M: Experimental Immunochemistry, 2nd ed. Springfield, Illinois, Charles C Thomas, 1961
Steer ML: Workshop on experimental pancreatitis. Dig Dis Sci 30:575–581, 1985
Bjork I, Danielsson A: Antithrombin and related inhibitors of coagulation proteinases.In Proteinase Inhibitors. Barrett, Salvesen (eds). Amsterdam, Elsevier, 1986, pp 489–513
Koide T: Isolation and characterization of antithrombin III from human, porcine and rabbit plasma and rat serum. J Biochem 86:1841–1850, 1979
Bauer KA, Rosenberg RD: Congenital Antithrombin III deficiency: Insights into the pathogenesis of the hypercoagulable state and its management using markers of hemostatic system activation. Am J Med 87 (suppl 3B):39S-43S, 1989
Wardle EN: Fibrinogen and albumin catabolism in experimental pancreatitis in the rat. J Surg Res 15:122, 1973
Ranson JHC, Lackner H, Berman IR, Schinella R: The relationship of coagulation factors to clinical complications of acute pancreatitis. Surgery 81:502–511, 1977
Danielsson A, Bjork I: Mechanism of inactivation of trypsin by antithrombin. Biochem J 207:21–28, 1982
Gabryelewicz A, Kosidlo S, Prokopowicz J, Podkowicz K: Does heparin modify protease-antiprotease balance in acute experimental pancreatitis in rats. Hapato-Gastroenterol 33:79–82, 1986
Vinazzer H: Clinical use of antithrombin III concentrates. Vox Sang 53:193–198, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bleeker, W.K., Agterberg, J., Rigter, G. et al. Protective effect of antithrombin III in acute experimental pancreatitis in rats. Digest Dis Sci 37, 280–285 (1992). https://doi.org/10.1007/BF01308184
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01308184