Repetitive short-term obstructions of the common bile-pancreatic duct induce severe acute pancreatitis in the opossum

Gallstone pancreatitis is triggered by migrating stones that cause transient or continuous bile-pancreatic duct obstruction. One might hypothesize that the great clinical variability of acute pancreatitis is related to the inconsistent number and duration of a series of stone migrations. A new setting for the opossum model of acute pancreatitis was developed allowing reversible bile-pancreatic duct obstructions. We compared the effects, on the pancreas and pancreatitis severity, of repeated transient obstructions to those of continuous obstruction of varying duration. Repetitive intermittent duct obstruction in American opossums was achieved using an extraductal balloon occluder connected to a subcutaneous port system that was inflated three times for 24 hr within a five-day period. Continuous duct obstruction was achieved by duct ligation. Sham-operated animals served as controls. After one, three, or five days of continuous obstruction and at the end of the third consecutive 24-hr obstruction (day 5), animals were killed and the severity of pancreatitis was determined quantitating the extent of acinar cell necrosis, pancreatic edema, and acinar cell fragility. Three repetitive one-day periods (total 72 hr) of bile-pancreatic duct obstruction resulted in acute necrotizing pancreatitis. The severity of pancreatitis was similar to that observed after five days of continuous obstruction and was more severe than that noted after three days (72 hr) of continuous obstruction. In conclusion, these observations suggest that the pancreas is susceptible to sensitization by factors related to transient duct obstruction. A series of minor events such as repeated stone passage may thus contribute to the progression to severe pancreatitis.