ISCHEMIA-REPERFUSION OF THE PANCREAS - A NEW IN-VIVO MODEL FOR ACUTE-PANCREATITIS IN RATS

Based on the concept that ischemia is an important factor in the patho genesis of acute pancreatitis, we developed a new model of complete is chemia/reperfusion of the pancreas in the rat. The aim of this study w as to investigate the microcirculation of the pancreas after complete and reversible ischemia at different times after reperfusion by using intravital fluorescence microscopy. In addition, the effect of ischemi a/reperfusion on the pancreas was assessed by means of light and elect ron microscopy and measurement of serum pancreas amylase concentration . In 35 adult Sprague-Dawley rats ischemia of the pancreas was induced by temporary occlusion of the four supplying arteries. Sham-operated animals served as controls (group A). After periods of 30 min (group B ), 60 min (group C) or 120 min (group D) of ischemia the organ was rep erfused. To exclude the influence of hypovolemia on microcirculation i n group E (120 min ischemia) hydroxyethyfstarch (HES) was given i.v. t o maintain central venous pressure at baseline values. For intravital fluorescence microscopy the pancreas was exteriorized on a stage and q uantitative analysis of microcirculation, including functional capilla ry density and leukocyte-endothelium interaction, was performed after 30 min, 1 h and 2 h of reperfusion. Serum pancreas-amylase was measure d at control (prior ischemia) and at 2 h after reperfusion. Tissue sam ples for light and electron microscopy were taken 2 h after reperfusio n. In sham-operated animals, functional capillary density (FCD) remain ed within baseline values (FCD 407.7 +/- 9 cm(-1)) during reperfusion. Dependent on the time of ischemia and time of reperfusion a gradual r eduction in functional capillary density was observed; after 2 h of is chemia only 35% of capillaries were perfused (FCD 140.9 +/- 28.3 cm(-1 )). Reduced functional capillary density was associated with an increa se of perfusion heterogeneity to a maximum of 0.65 +/- 0.12, as agains t 0.13 +/- 0.02 in central animals. With a 2 h ischemia leukocyte-endo thelium interaction was enhanced after 0.5 h of reperfusion (8-fold in crease of adherent leukocytes in comparison to control) followed by a further significant increase until 2 h after the beginning of reperfus ion. Amylase concentration after ischemia of 2 h (2967 +/- 289 U/l) wa s significantly higher as compared to controls (1857 +/- 99 U/l). Diff erences between group E and D were not observed. Pancreatic tissue inj ury was ascertained by histopathological studies. These results indica te that complete ischemia/reperfusion of the pancreas induces pancreat ic microvascular failure. The severity of changes depends on duration of ischemia and duration of reperfusion. The morphological and biochem ical changes suggest that ischemia/reperfusion causes an inflammatory reaction as observed in acute pancreatitis.