Abstracts
1998 Digestive Disease Week

#1015

MATRIX METALLOPROTEINASE (MMP) 2 AND 9 ACTIVITY IN EXPERIMENTAL ACUTE PANCREATITIS. S. Patel, J. Schwartz, N. Chaung, S. G. Marcus, H. L. Pachter, E. Deutsch, A. C. Galloway, K. Eng, P. Mignatti, P. Shamamian. S. Arthur Localio Laboratory, Department of Surgery, NYU Medical Center, NY, NY.

Background: In severe acute pancreatitis (AP) there is extensive injury to the parenchyma with destruction of pancreatic architecture. Peritoneal fluid samples obtained from animals with experimental AP contain enzymes, proteinases and inflammatory mediators, which have been implicated in the pathophysiology of pancreatic injury. MMPs are a zinc containing family of proteinases, which play a key role in extracellular matrix degradation during tumor invasion, angiogenesis, and neutrophil/monocyte diapedesis. All MMP family members are synthesized and secreted as inactive zymogen precursors that are activated by limited proteolysis. The role of MMPs in pancreatic injury following AP has not been investigated. We hypothesize that MMPs may be involved in the pancreatic parenchymal destruction seen during AP.Methods: A midline laparotomy was performed on Sprague-Dawley rats (n=15) which were randomized into the following experimental groups: Sham, Normal Saline (NS), or 5% Taurocholic Acid (5% TA). The pancreatic duct was identified and injected with either 1 ml of NS or 5% TA. The animals were sacrificed 12 hrs after induction of pancreatitis. Pancreatic injury was evaluated on Hematozylin and Eosin stained tissue specimens. Serum was analyzed for amylase. Peritoneal lavage was performed with 10 ml of NS; 1-ml aliquots of which were analyzed by gelatin zymography. Gelatin zymograms were analyzed by densitometry using NIH image analyzer and are expressed in density units (DU). Data is reported as mean ± sem. Statistical analysis was performed using ANOVA and correlation was determined by computing Pearson's correlation coefficient. Results: Animals which had
5% TA injected into the pancreatic duct had consistently more severe pancreatic injury compared to NS injected animals.

Peritoneal washings from animals with pancreatitis show significantly higher levels of active MMP 2 and 9 compared to sham and NS injected animals (*p<. 01). There is significant correlation between serum amylase and active MMP 2 and 9 levels (p<. 01). Conclusion: This study demonstrates the presence of active MMP 2 and 9 in the peritoneal washings of animals with AP. We have established a correlation between active amounts of MMP 2 and 9 in peritoneal washings with the severity of AP. MMP 2 and 9 may be important for the egress of PMNs and monocytes from the vascular space into the pancreatic parenchyma and the consequent tissue destruction.

Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.