Abstracts
2002 Digestive Disease Week

# 106598 Abstract ID: 106598 Alcoholic Pancreatitis: New Strategies of Prophylaxis and Therapy
Jens Werner, Werner Hartwig, Thilo Hackert, Jan Schmidt, Eduard Ryschich, Martha M Gebhard, Ernst Klar, 69120 Heidelberg, Germany

Alcohol is the leading cause of acute pancreatitis. However, even today specific prophylactic or therapeutic regimens of alcoholic pancreatitis do not exist. We evaluated different strategies for prophylaxis and therapy of alcoholic pancreatitis (AP) in Wistar-rats. Methods: We induced AP by infusion of ethanol together with two cofactors of alcoholic pancreatitis, lipid infusion (hyperlipidemia) and a temporary pancreatic duct obstruction (2hrs). Rats received the following medications either prophylactically or as a therapeutic approach 3 hrs after induction of AP (n=6/group): Protease inhibitors: 1. trypsinogen inhibor (TI), 2. gabexate mesilate (GM); oxygen free radical scavengers: 3. acetylcystein (AC), 4. 4-Hydroxy TEMPO; 5. NO donor L-arginine (LA); 6. PAF-antagonist (PAF); 7. monoclonal antibodies against ICAM-1 (ICAM-1 AB); 8. Ringer (control group). Pancretic injury was assessed 12 hrs after the AP was induced by amylase, ectopic trypsinogen activation (TAP), myeloperoxidase and histology. In additional animals pancreatic microcirculation was assessed by intravital microscopy (perfusion, leukocyte adhesion). Results: Prophylactic administration of all medications (oxygen free radical scavengers AC and 4HT, NO, PAF and ICAM-1 AB) apart from the two protease inhibitors reduced the pancreatic injury of AP significantly (p<0.05; edema, TAP, inflammation, histology). While TI and GM, the two protease inhibitors did not have any effects on the pancreatic microcirculation, all other medications normalized pancreatic microcirculation even after induction of AP. However, only ICAM-1 AB normalized pancreatic perfusion, reduced leukocyte adhesion (p<0.001 vs. control) and the degree of pancreatitis (p<0.01 vs control) when applied with a therapy free interval of 3 hrs. Conclusion: Anti-ICAM-1 is an effective treatment of acute alcoholic pancreatitis, while oxygen free radical scavengers, NO and PAF are not. In contrast, prophylactic application of those therapeutic agents which are directed against initial pathogenetic steps of pancreatitis prevent alcoholic pancreatitis. The prophylactic inhibition of oxygen free radicals seems most practicable in the prevention of alcoholic pancreatitis.