Hyperoncotic ultrahigh molecular weigh dextran solutions reduce trypsinogen activation, prevent acinar necrosis, and lower mortality in rodent pancreatitis

Acinar necrosis in patients with acute pancreatitis can be due to enzymatie injury, ischemia, or both. We hypothesized that novel therapy aimed at an improvement of pancreatic microcirculation early in the course of pancreatitis may reduce the lethality and aeinar damage. Forty-six dextran-resistant rats received controlled intraductal infusion of glycodeoxycholic acid (10 mmol/L), followed by intravenous cerulein ( 5 [micro]g/kg/h) for 6 hours. Beginning 30 minutes after the induction of pancreatitis, all animals were resuscitated with Ringer's lactate (RL) (8 mL/kg/h intravenously for 9 hours . In addition, they were given intra-aortic bolus infusions (2 mL/kg at 30, 60, 90, and 150 minutes) of either RL, sodium chloride (NaCI) (7.5%) and dextran 60,000 (10%) (HHS-60), NaCI (7.5%) and dextran 500,000 (10%) (HHS-500), or NaCl (0.9%) and dextran 500,000 (10%) (DEX-500). Despite high-volume fluid resuscitation in the group that received RL and HHS-60, 70% of the animals in each of these groups died within 24 hours. In contrast, the mortality rates in the groups of animals that received HHS-500 and DEX-500 were dramatically reduced to 0% and 10%, respectively (p= 0.005, p = 0.02). Histopathologic scores for aeinar necrosis were significantly lower in the group of animals that received DEX-500 (p Rapid bolus infusion of hyperoncotic ultra-high molecular weight dextran solution with or without hypertonic saline but not RL or hypertonic-hyperoneotic saline-dextran significantly reduced pathologic trypsinogen activation, prevented acinar necrosis, and improved survival in acute experimental pancreatitis. We speculate that a sustained improvement of pancreatic microcirculation by ultrahigh molecular weight dextran is the mechanism of action.