EFFECTS OF BILE AND PANCREATIC DIGESTIVE ENZYMES ON PERMEABILITY OF THE PANCREATIC DUCT SYSTEM IN RABBITS

In order to reproduce what may occur during the initial phase of bilia ry acute pancreatitis, the rabbit pancreatic duct was perfused with pr eincubated mixtures of bile and different digestive enzymes at low phy siologic pressure. Permeability of the pancreatic duct system, serum a mylase, and histological appearance of pancreatic tissue were studied after orthograde duct perfusion in the anesthetized animal. The ductal permeability was estimated by recovery of fluoresceinated dextran (mo lecular weight 17,200) in central venous blood following duct perfusio n with this substance. Perfusion with preincubated bile failed to incr ease permeability significantly (11.10 +/- 3.04 nmol/L compared to 5.8 0 +/- 2.71 nmol/L in the control group), whereas mixtures of bile and trypsin (27.19 +/- 5.21 nmol/L), bile and lipase (16.68 +/- 3.75 nmol/ L), and bile and pancreatic juice (13.92 +/- 0.48 nmol/L) caused signi ficant increases (p < 0.05). Similar observations were made regarding serum amylase and histology. Thus, the presence of mixtures of bile wi th pancreatic enzymes (following their prolonged common incubation) in the absence of elevated pressure, results in an increase in duct perm eability for molecules up to the size range of pancreatic enzymes and thereby may contribute to the initiation of acute pancreatitis.