A better model of acute pancreatitis for evaluating therapy

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

Research output: Contribution to journalArticle

578 Citations (Scopus)

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

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Glycodeoxycholic Acid
Ceruletide
Pancreatitis
Wounds and Injuries
Bile Acids and Salts
Inflammation
Investigational Therapies
Therapeutics
Sprague Dawley Rats
Edema
Necrosis
Hemorrhage
Pressure
Mortality

ASJC Scopus subject areas

  • Surgery

Cite this

Schmidt, J., Rattner, D. W., Lewandrowski, K., Compton, 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.

A better model of acute pancreatitis for evaluating therapy. / Schmidt, Jan; Rattner, David W.; Lewandrowski, Kent; Compton, Carolyn; Mandavilli, Uma; Knoefel, Wolfram T.; Warshaw, Andrew L.

In: Annals of Surgery, Vol. 215, No. 1, 1992, p. 44-56.

Research output: Contribution to journalArticle

Schmidt, J, Rattner, DW, Lewandrowski, K, Compton, C, Mandavilli, U, Knoefel, WT & Warshaw, AL 1992, 'A better model of acute pancreatitis for evaluating therapy', Annals of Surgery, vol. 215, no. 1, pp. 44-56.
Schmidt J, Rattner DW, Lewandrowski K, Compton C, Mandavilli U, Knoefel WT et al. A better model of acute pancreatitis for evaluating therapy. Annals of Surgery. 1992;215(1):44-56.
Schmidt, Jan ; Rattner, David W. ; Lewandrowski, Kent ; Compton, Carolyn ; Mandavilli, Uma ; Knoefel, Wolfram T. ; Warshaw, Andrew L. / A better model of acute pancreatitis for evaluating therapy. In: Annals of Surgery. 1992 ; Vol. 215, No. 1. pp. 44-56.
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