INCREASED INTRAPANCREATIC TRYPSINOGEN ACTIVATION IN ISCHEMIA-INDUCED EXPERIMENTAL PANCREATITIS

Objective The potential of pancreatic ischemia to cause acute pancreat itis as indicated by morphologic changes and ectopic trypsinogen activ ation was investigated. Background Experimental evidence has shown tha t pancreatic ischemia is important in the evolution of severe pancreat itis, but whether ischemia can initiate pancreatitis has been disputed . Methods Pancreatic ischemia was induced in rats by hemorrhagic hypot ension (30 mm Hg for 30 min; n = 64). Changes of pancreatic microcircu latory perfusion were studied using diffuse reflectance spectroscopy. Serum amylase, trypsinogen activation peptide (TAP) in serum and pancr eatic tissue, wet/dry weight ratio, and histology were determined over 24 hours and compared with sham-operated control subjects (n = 35). R esults 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/dr y weight ratio (2.8 +/- 0.1), and histology remained unchanged. Tempor ary hypotension markedly decreased pancreatic perfusion with incomplet e 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 nmo l/L X g, p < 0.05)and increased to 341 +/- 43 nmol/L X g (p < 0.001) a fter 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 addit ion to its potentiating role, severe pancreatic ischemia can play a pa thogenetic role in the initiation of acute pancreatitis.