A better model of acute pancreatitis for evaluating therapy.
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 less than 0.0005), acinar necrosis (p less than 0.01), inflammation (p less than 0.006), and hemorrhage (p less than 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.
Schmidt
J
J
Departments of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Rattner
D W
DW
Lewandrowski
K
K
Compton
C C
CC
Mandavilli
U
U
Knoefel
W T
WT
Warshaw
A L
AL
D000208:Acute Disease; D000818:Animals; D001774:Blood Chemical Analysis; D002108:Ceruletide / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D006002:Glycodeoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D010179:Pancreas / Q000473:pathology; D010183:Pancreatic Ducts; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D006002:Glycodeoxycholic Acid; D002108:Ceruletide