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. 1995 Apr;221(4):364–371. doi: 10.1097/00000658-199504000-00006

Increased intrapancreatic trypsinogen activation in ischemia-induced experimental pancreatitis.

K Mithöfer 1, C Fernández-del Castillo 1, T W Frick 1, T Foitzik 1, D G Bassi 1, K B Lewandrowski 1, D W Rattner 1, A L Warshaw 1
PMCID: PMC1234585  PMID: 7537036

Abstract

OBJECTIVE: The potential of pancreatic ischemia to cause acute pancreatitis as indicated by morphologic changes and ectopic trypsinogen activation was investigated. BACKGROUND: Experimental evidence has shown that pancreatic ischemia is important in the evolution of severe pancreatitis, but whether ischemia can initiate pancreatitis has been disputed. METHODS: Pancreatic ischemia was induced in rats by hemorrhagic hypotension (30 mm Hg for 30 min; n = 64). Changes of pancreatic microcirculatory perfusion were studied using diffuse reflectance spectroscopy. Serum amylase, trypsinogen activation peptide (TAP) in serum and pancreatic tissue, wet/dry weight ratio, and histology were determined over 24 hours and compared with sham-operated control subjects (n = 35). RESULTS: In control animals, serum amylase (47.9 +/- 2.1 units/L), serum (7.9 +/- 0.7 nmol/L) and tissue TAP (63.0 +/- 5.4 nmol/L x g), wet/dry weight ratio (2.8 +/- 0.1), and histology remained unchanged. Temporary hypotension markedly decreased pancreatic perfusion with incomplete recovery after reperfusion. Pancreatic isoamylase activity increased within 1 hour (110 +/- 5 units/L, p < 0.05) and further to 151 +/- 18 units/L at 24 hours. Tissue TAP was elevated at 1 hour (134 +/- 16 nmol/L x g, p < 0.05) and increased to 341 +/- 43 nmol/L x g (p < 0.001) after 24 hours, whereas serum TAP remained unchanged (8.3 +/- 0.5 nmol/L). Morphologic alterations included elevated wet/dry weight ratio (4.1 +/- 0.3, p < 0.01) and increased histologic scores for edema (p < 0.05) and acinar necrosis (p < 0.05) at 24 hours. Trypsinogen activation preceded the development of pancreatic necrosis. CONCLUSIONS: In addition to its potentiating role, severe pancreatic ischemia can play a pathogenetic role in the initiation of acute pancreatitis.

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Selected References

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