Caerulein or taurocholate induced enzymatic and histologic alterations in the isolated perfused rat pancreas.
BACKGROUND
Early events in the pathogenesis of experimental acute pancreatitis are intensively studied using isolated cells or animal models. However, the results and their interpretations are dependent on the complexity of biological structures. Therefore, we proposed that studies on isolated perfused pancreas can give additional information about processes leading to acinar cell injury. This hypothesis was examined adapting the well-established caerulein hyperstimulation model and the taurocholate model of acute pancreatitis to the extracorporeal perfused isolated rat pancreas.


METHODS
The pancreas was removed with the duodenum including the arterial supply. A continuous perfusion of the organ was performed with a modified Krebs-Ringer bicarbonate buffer. Intraarterial caerulein application or an intraductal taurocholate (3.5%) application were used to induce acinar cell injury which was determined as the release of amylase, lipase and lactate dehydrogenase into the portal outflow medium and into the transudation fluid and by examination of histological alterations. Trypsinogen release and activation was followed by analysis of trypsinogen activation peptide (TAP) in the transudation fluid and in pancreatic tissue.


RESULTS
Perfusion of isolated rat pancreas with supramaximal concentrations of caerulein or retrograde injection of taurocholate (3.5%) resulted in acinar cell injury indicated by elevated levels of amylase and lipase into the perfusate and into the transudation fluid. TAP levels in the transudation fluid significantly increased after perfusion with caerulein or retrograde injection of taurocholate (3.5%). The histological alterations after taurocholate application include oedema and necrosis and show significant differences to the control perfusion. Extensive pancreatic necroses were not observed after caerulein hyperstimulation.


CONCLUSIONS
The isolated perfused rat pancreas is a useful model to investigate pathophysiological mechanisms which are relevant for the early phase of acute pancreatitis. The caerulein and the taurocholate models are transferable to the isolated rat pancreas. Studies on isolated perfused rat pancreas enable pathophysiological investigations of the exocrine pancreas without influence of systemic components, but with preserved morphology.
Mantke
R
R
Department of General, Gastroenterological and Vascular Surgery, Otto von Guericke University, Magdeburg, Germany. mantke@klinikum-brandenburg.de
Schubert
D
D
Röcken
C
C
Paege
I
I
Halangk
W
W
Peters
B
B
Lippert
H
H
Schulz
H-U
HU
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002108:Ceruletide / Q000494:pharmacology*; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008049:Lipase / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced* / Q000473:pathology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D005765:Gastrointestinal Agents; D013656:Taurocholic Acid; D002108:Ceruletide; D008049:Lipase; D000681:Amylases