Repetitive Short-Term Obstructions of the Common Bile–Pancreatic Duct Induce Severe Acute Pancreatitis in the Opossum

Abstract

Gallstone pancreatitis is triggered by migratingstones that cause transient or continuousbile–pancreatic duct obstruction. One mighthypothesize that the great clinical variability of acutepancreatitis is related to the inconsistent number andduration of a series of stone migrations. A new settingfor the opossum model of acute pancreatitis wasdeveloped allowing reversible bile–pancreatic ductobstructions. We compared the effects, on the pancreas andpancreatitis severity, of repeated transientobstructions to those of continuous obstruction ofvarying duration. Repetitive intermittent ductobstruction in American opossums was achieved using anextraductal balloon occluder connected to a subcutaneousport system that was inflated three times for 24 hrwithin a five-day period. Continuous duct obstruction was achieved by duct ligation. Sham-operatedanimals served as controls. After one, three, or fivedays of continuous obstruction and at the end of thethird consecutive 24-hr obstruction (day 5), animals were killed and the severity of pancreatitiswas determined quantitating the extent of acinar cellnecrosis, pancreatic edema, and acinar cell fragility.Three repetitive one-day periods (total 72 hr) of bile–pancreatic duct obstruction resultedin acute necrotizing pancreatitis. The severity ofpancreatitis was similar to that observed after fivedays of continuous obstruction and was more severe than that noted after three days (72 hr) ofcontinuous obstruction. In conclusion, theseobservations suggest that the pancreas is susceptible tosensitization by factors related to transient ductobstruction. A series of minor events such as repeated stonepassage may thus contribute to the progression to severepancreatitis.