title: Enterokinase induces severe necrosis and rapid mortality in cerulein pancreatitis: characterization of a novel noninvasive rat model of necro-hemorrhagic pancreatitis.
abstract: BACKGROUND
  Unlike edematous pancreatitis, induction of severe necrotizing pancreatitis in rats generally requires an invasive laparotomy with infusion and/or ligation of the pancreatic duct or duodenal or arterial occlusion. The aim of this study was to establish and characterize a noninvasive model of severe acute pancreatitis in rats.
  
  
  METHODS
  Wistar rats were infused intravenously with cerulein or a combination of cerulein and enterokinase. Saline (154-mmol/L NaCl) or enterokinase only was infused in controls. In a first set of experiments, intrapancreatic protease activation and the release of cytokines were correlated with the severity of organ injury. Pancreatic and pulmonary injuries were determined at 6 h. In a second set of experiments, we assessed 24-h survival, serum parameters possibly reflecting the course of the disease, and morphologic changes later in the course of the disease.
  
  
  RESULTS
  The severity of pancreatic injury and survival were correlated strongly with the amount of enterokinase infused simultaneously with cerulein. Trypsin as well as elastase and cathepsin B activity in pancreatic tissue samples were increased markedly in these animals. Marked pancreatic hemorrhage, necrosis, and leukocyte infiltration were present in animals with the greatest amounts of enterokinase infused. IL-6 and LDH, but not IL-1beta, CRP, and amylase, in serum correlated with the severity of pancreatitis.
  
  
  CONCLUSIONS
  This noninvasive rat model of acute pancreatitis is characterized by major pancreatic necrosis, hemorrhage, and fatality. The simple and noninvasive induction technique may have advantages for future studies on inflammatory changes and sepsis in necrotizing pancreatitis compared with other currently available invasive models.
authors.affiliation: Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hartwig
authors.forename: Mareike
authors.initials: M
authors.lastname: Kolvenbach
authors.forename: Thilo
authors.initials: T
authors.lastname: Hackert
authors.forename: Franco
authors.initials: F
authors.lastname: Fortunato
authors.forename: Lutz
authors.initials: L
authors.lastname: Schneider
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D002108:Ceruletide; D004195:Disease Models, Animal; D004338:Drug Combinations; D004765:Enteropeptidase / Q000009:adverse effects*; D015850:Interleukin-6 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010196:Pancreatic Elastase / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
chemical_list: D004338:Drug Combinations; D015850:Interleukin-6; D002108:Ceruletide; D007770:L-Lactate Dehydrogenase; D010196:Pancreatic Elastase; D004765:Enteropeptidase; D002401:Cathepsin B