A better model of acute pancreatitis for evaluating therapy

Jan Schmidt, David W. Rattner, Kent Lewandrowski, Carolyn C. Compton, Uma Mandavilli, Wolfram T. Knoefel, Andrew L. Warshaw

Research output: Contribution to journalArticle

Abstract

Existing models of acute pancreatitis have limitations to studying novel therapy. Whereas some produce mild self-limited pancreatitis, others result in sudden necrotizing injury. The authors developed an improved model providing homogeneous moderately severe injury by superimposing secretory hyperstimulation on minimal intraductal bile acid exposure. Sprague-Dawley rats (n = 231) received low-pressure intraductal glycodeoxycholic acid (GDOC) at very low (5 or 10 mmol/L) concentrations followed by intravenous cerulein. Cerulein or GDOC alone caused only very mild inflammation. However, GDOC combined with cerulein was uniformly associated with more edema (p <0.0005), acinar necrosis (p <0.01), inflammation (p <0.006), and hemorrhage (p <0.01). Pancreatic injury was further increased and death was potentiated by increasing volume and duration of intraductal low-dose GDOC infusion. There was significant morphologic progression between 6 and 24 hours. The authors conclude that (1) combining minimal intraductal bile acid exposure with intravenous hyperstimulation produces homogeneous pancreatitis of intermediate severity that can be modulated at will; (2) the injury is progressive over at least 24 hours with finite mortality rate; (3) the model provides superior opportunity to study innovative therapy.

Original languageEnglish (US)
Pages (from-to)44-56
Number of pages13
JournalAnnals of Surgery
Volume215
Issue number1
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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    Schmidt, J., Rattner, D. W., Lewandrowski, K., Compton, C. C., Mandavilli, U., Knoefel, W. T., & Warshaw, A. L. (1992). A better model of acute pancreatitis for evaluating therapy. Annals of Surgery, 215(1), 44-56.