BENEFITS OF VARIOUS DEXTRANS AFTER DELAYED THERAPY IN NECROTIZING PANCREATITIS OF THE RAT

Objective: Ultrahigh-molecular dextran (500 000 Da) has been shown to prevent pancreatic necrosis when given 30 min after induction of pancr eatitis. This study should clarify the following: (a) are dextrans sti ll effective after prolongation of the therapy-free interval? (b) what is the impact of the molecular weight of the dextrans? and (c) is the ir effect influenced by the dextran concentration or by the addition o f hypertonic saline? Animals and interventions: Acute pancreatitis was induced in 70 male dextran-tolerant Wistar rats using intraductal bil e-salt infusion and intravenous hyperstimulation. After 3 h, animals w ere assigned to one of seven groups (n = 10 per group) receiving eithe r Ringer solution or different dextrans (10%) including 70 000 Da (DEX -70), 160 000 Da (DEX-160), 300 000 Da (DEX-300) or 500 000 Da (DEX-50 0). Additional groups included DEX-70 (6%) and DEX-70 (10%) in combina tion with hypertonic NaCl (7.5%) (HHS-70). Ringer solution was given a t 24 ml/kg and all dextrans at 8 ml/kg. Measurements and results: Tryp sinogen activation peptides (TAP) were quantified in ascites and acina r necrosis after death or sacrifice at 9 h. As an index of less pathol ogical trypsinogen activation, the mean TAP levels in ascites were sig nificantly lower in DEX-70 and DEX-160 compared to Ringer controls (p < 0.05, t-test). Furthermore, the amount of acinar necrosis was signif icantly lower in all dextran groups except the HHS-70 in comparison wi th Ringer controls (p < 0.01, t-test). Finally, mortality was signific antly reduced from 60% in Ringer controls to 10 and 0%, respectively, in the groups treated with DEX-70 and DEX-160 (p<0.03, Fisher's Exact test). There was a similar trend in all other groups except the HHS-70 . Conclusions: Despite a therapy-free interval of 3 h, dextrans reduce trypsinogen activation, prevent acinar necrosis, and improve survival in necrotizing rodent pancreatitis. The molecular weight and concentr ation of dextran are of secondary importance for these beneficial effe cts.