Abstracts
2002 Digestive Disease Week

# 105587 Abstract ID: 105587 Cyclosporin Aggravates Tissue Damage in Ischemia-Induced Acute Pancreatitis.
Thilo Hackert, Jens Werner, Thorsten Löffler, Werner Hartwig, Martha M Gebhard, Ernst Klar, 69120 Heidelberg, Germany

Background: Ischemia-reperfusion associated mechanisms are the major pathogenetic factors in the development of posttransplant-pancreatitis which is one of the major complications following pancreas transplantation. The influence of immunosuppressants on graft pancreatitis remains unclear. Aim of our study was to evaluate the effects of FK 506 and ciclosporin in an experimental model of warm pancreatic ischemia-reperfusion. Methods: In 18 Wistar rats warm pancreatic ischemia was induced by cross-clamping of pancreatic vessels for1 hour followed by reperfusion for 24 hours. After this period the following parameters were evaluated: serum amylase, serum endothelin 1 levels, histological damage:(HE slides, score 0-3 for edema, inflammation and necrosis). Animals were divided into 3 groups (each n=6): 1) control animals (Ringers solution), 2) FK 506 (5 mg/kg) 30 min. before reperfusion, 3) ciclosporin (10 mg/kg) 30 min. before reperfusion. Results: In all animals serum amylase was significantly higher after pancreatic ischemia compared to baseline values (p<0,05). In ciclosporin treated animals amylase levels were significantly (p<0,05) higher compared to control and FK 506 animals (9290+/-1384 u/l vs 3453+/-1013 and 3496+/-755 u/l). Endothelin 1 levels were comparable in control and FK506 animals (0,5+/-0,13 vs 0,54+/-0,2 fmol/ml) and showed a tendency towards higher levels in ciclosporin animals without reaching statistical significance (0,9+/-0,35 fmol/ml; p=0,11). Histological examination showed a comparable extent of damage in control and FK 506 animals (inflammation 0,58+/-0,08 vs 0,38+/-0,13, necrosis 0,42+/-0,08 vs 0,38+/-0,07). In ciclosporin animals inflammation (1,5+/-0,15) and necrosis (1,55+/-0,15) were significantly higher compared to the two other groups(p<0,05). Conclusion: Ciclosporin aggravates tissue damage in our experimental model of ischemia-induced pancreatic damage. These changes might be mediated via an upregulation of endothelin 1. Further studies are neccessary to elucidate the underlying mechanisms and evaluate these effects in a model of pancreatic transplantation.