Pancreatic and bile duct obstruction exacerbates rat caerulein-induced pancreatitis: a new experimental model of acute hemorrhagic pancreatitis.
BACKGROUND
Pancreatic duct obstruction induces edematous but not hemorrhagic pancreatitis even when combined with maximal secretory stimulation. The aim of the present study was to test the hypothesis that pancreatic and bile duct obstruction exacerbates edematous pancreatitis induced by supramaximal secretory stimulation by caerulein.


METHODS
In in vivo studies using rats, biliopancreatic duct ligation was combined with supramaximal stimulation of caerulein, and pancreatic histology, serum amylase level, pancreatic edema, and intrapancreatic trypsin activation were evaluated. In in vitro studies, the pancreatic acini were isolated from the rats with biliopancreatic duct ligation, and amylase secretion, intracellular trypsin activation, and acinar cell fragility were evaluated.


RESULTS
Biliopancreatic duct ligation exacerbated caerulein-induced pancreatitis from edematous to hemorrhagic only when the obstruction preceded caerulein administration. The amylase secretion from the acini was inhibited, and intracellular trypsin activation and the acinar cell fragility on the supramaximal stimulation with cholecystokinin in vitro were enhanced by the preceding in vivo biliopancreatic duct obstruction.


CONCLUSIONS
Preceding biliopancreatic duct obstruction exacerbates caerulein-induced pancreatitis. Enhancement of intracellular trypsin activation is possibly involved in this mechanism.
Yamasaki
Mitsuo
M
Department of Surgery, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-sayama 595-8511, Japan.
Takeyama
Yoshifumi
Y
Shinkai
Masayuki
M
Ohyanagi
Harumasa
H
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D002766:Cholecystokinin / Q000494:pharmacology; D002779:Cholestasis / Q000378:metabolism / Q000473:pathology*; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D018450:Disease Progression; D006470:Hemorrhage / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010183:Pancreatic Ducts; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000378:metabolism
D002108:Ceruletide; D002766:Cholecystokinin; D000681:Amylases; D014357:Trypsin