Increased intrapancreatic trypsinogen activation in ischemia-induced experimental pancreatitis.
OBJECTIVE
The potential of pancreatic ischemia to cause acute pancreatitis as indicated by morphologic changes and ectopic trypsinogen activation was investigated.


BACKGROUND
Experimental evidence has shown that pancreatic ischemia is important in the evolution of severe pancreatitis, but whether ischemia can initiate pancreatitis has been disputed.


METHODS
Pancreatic ischemia was induced in rats by hemorrhagic hypotension (30 mm Hg for 30 min; n = 64). Changes of pancreatic microcirculatory perfusion were studied using diffuse reflectance spectroscopy. Serum amylase, trypsinogen activation peptide (TAP) in serum and pancreatic tissue, wet/dry weight ratio, and histology were determined over 24 hours and compared with sham-operated control subjects (n = 35).


RESULTS
In control animals, serum amylase (47.9 +/- 2.1 units/L), serum (7.9 +/- 0.7 nmol/L) and tissue TAP (63.0 +/- 5.4 nmol/L x g), wet/dry weight ratio (2.8 +/- 0.1), and histology remained unchanged. Temporary hypotension markedly decreased pancreatic perfusion with incomplete recovery after reperfusion. Pancreatic isoamylase activity increased within 1 hour (110 +/- 5 units/L, p < 0.05) and further to 151 +/- 18 units/L at 24 hours. Tissue TAP was elevated at 1 hour (134 +/- 16 nmol/L x g, p < 0.05) and increased to 341 +/- 43 nmol/L x g (p < 0.001) after 24 hours, whereas serum TAP remained unchanged (8.3 +/- 0.5 nmol/L). Morphologic alterations included elevated wet/dry weight ratio (4.1 +/- 0.3, p < 0.01) and increased histologic scores for edema (p < 0.05) and acinar necrosis (p < 0.05) at 24 hours. Trypsinogen activation preceded the development of pancreatic necrosis.


CONCLUSIONS
In addition to its potentiating role, severe pancreatic ischemia can play a pathogenetic role in the initiation of acute pancreatitis.
Mithöfer
K
K
Department of Surgery, Massachusetts General Hospital, Boston, USA.
Fernández-del Castillo
C
C
Frick
T W
TW
Foitzik
T
T
Bassi
D G
DG
Lewandrowski
K B
KB
Rattner
D W
DW
Warshaw
A L
AL
D000681:Amylases / Q000097:blood; D000818:Animals; D007511:Ischemia / Q000150:complications*; D007517:Isoamylase / Q000097:blood; D008297:Male; D010179:Pancreas / Q000098:blood supply*; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014362:Trypsinogen / Q000378:metabolism*
D014362:Trypsinogen; D000681:Amylases; D007517:Isoamylase