Abstracts
2002 Digestive Disease Week

# 108172 Abstract ID: 108172 Inosine Reduces Ischemia/Reperfusion Damage in a Model of Pancreatic Warm Ischemia/Reperfusion
Thorsten Loeffler, Jens Werner, Jan Schmidt, Martha M Gebhard, Ernst Klar, 69120 Heidelberg, Germany

Purpose: Former studies showed that ischemia/ reperfusion damage correlates with inflammatory response following expression of proinflammatory cytokines and microcirculatory disturbances. Aim of this study was to quantify microcircularory disturbances and tissue damage in a model of pancreatic warm ischemia of the rat and to examine the influence of inosine, a immunomodulatory substance, on this cascade. Materials And Methods: We performed reversible warm ischemia of the pancreas in 20 Wistar rats (291 g) by clamping the 4 supplying arteries and defined experimental groups as follows (beginning of infusion immediately after clamping): (1) 1 h ischemia/ infusion of saline for 6 h, (2) 1,5 h ischemia/ saline, (3) 2 h ischemia/ saline, (4) 1 h ischemia/ infusion of inosine (100 mg/kg) for 6 h, (5) 2 h ischemia/ inosine. The Pancreas was removed 12 h after reperfusion and the level of edema, inflammation and necrosis was quantified by a histological score (0-3). Furthermore 4 animals in each group ((6) 2 h ischemia/ saline, (7) 2 h ischemia/ inosine) were examined 6 h after reperfusion by intravitalmicroscopy for changes in red blood cell velocity and leukocyte endothelial interaction. Results: Tissue damage increased depending on the duration of ischemia: 1 h of ischemia induced mild pancreatitis, severe pancreatitis was recorded after 2 h of ischemia with necrosis and inflammatory infiltration. Administration of inosine resulted in significant improvement of tissue damage (p<0,01) in group (4) vs. group (1) and in group (5) vs. group (3) especially regarding inflammation and necrosis. Mean capillary red blood cell velocity as a marker of perfusion was increased from 0,44 mm/s (6) to 0,82 mm/s (7) (p<0,05). The number of adherent leukocytes per 100 microm was reduced from 6,3 (6) to 2,3 (7). Conclusion: In the model of pancreatic warm ischemia/ reperfusion of the rat damage is paralleled by microcirculatory disturbance, an increased leukocyte endothelial interaction and necrosis. The changes are moderate after 1 h of ischemia, severe after 2 h of ischemia. Microcirculatory disturbance and tissue damage are improved by administration of inosine, possibly by modulating the expression of cytokines.