HYPERONCOTIC DEXTRAN AND SYSTEMIC APROTININ IN NECROTIZING RODENT PANCREATITIS

Background: Dextrans improve pancreatic microcirculation in acute expe rimental pancreatitis. They could therefore facilitate the transport o f a protease inhibitor to ischemic areas of tissue injury and be of ad ditional benefit. Methods: To compare the effects of dextrans with and without aprotinin, necrotizing pancreatitis was induced in 33 male de xtran-resistant Wistar rats by intraductal infusion of low-dose glycod eoxycholic acid (10 mmol/l) followed by intravenous cerulein (5 mu g/k g/h) for 6 h. Three and four hours after the start of the cerulein inf usion the animals received infusions of either Ringer's lactate (RL) ( 12 ml/kg), 70,000 Da dextran (10%) (DEX-70) (4 ml/kg) alone, or DEX-70 (4 ml/kg) with aprotinin (5000 IU/kg) (DEX-70/A). Results: The death rate was 60% within 9 h in the RL group (6 of 10) but only 10% in the DEX-70 group (1 of 10) (p < 0.03; Fisher's exact test) and 23% in the DEX-70/A group (3 of 13). Histomorphometry demonstrated a significant reduction of acinar necrosis in both treatment groups compared with co ntrol animals (p < 0.014; t test). Total amounts of trypsinogen activa tion peptides (TAP) in ascites were also significantly lower in these groups (p < 0.05; t test). Conclusions: DEX-70 given 3 h and 4 h after induction of pancreatitis significantly reduced the levels of TAP, li mited acinar necrosis, and improved survival rate in acute necrotizing rodent pancreatitis. There was no additional benefit from the combina tion with aprotinin.