Society for Surgery of the Alimentary Tract

Abstracts
1998 Digestive Disease Week

#1013

SEVERE HYPERSTIMULATION/OBSTRUCTION PANCREATITIS: A MODEL CHARACTERIZED BY ACINAR ATROPHY AND INTERSTITIAL PANCREATIC FIBROSIS. K. Murayama*, B. Barent+, A. Brooks+, M. Gruber+, S. Eliason@, E. Brunt@, G. Smith*. Depts of *Surgery and @Pathology, St. Louis University, St. Louis, MO and +Dept of Surgery, University of Nebraska Medical Center, Omaha, NE.

Significant fibrosis and acinar atrophy are characteristics of chronic pancreatitis, however, due to the lack of a reproducible model the acute phase of these changes is poorly understood. We have developed a model of severe hyperstimulation/
obstruction pancreatitis (SHOP) to better define the mechanisms of the early phase of pancreatic fibrogenesis.

METHODS: Sprague-Dawley rats were used and SHOP was induced in 15 rats by complete pancreatic duct obstruction and daily cerulein hyperstimulation (25 µg/kg, ip). Rats were sacrificed at 24h (n=4), 48h (n=4), 72h (n=3), and 96h (n=4). Controls underwent sham operation and received no cerulein. Pancreata were divided and prepared for H&E and sirius red staining (collagen specific), immunofluorescence microscopy (anti-human collagen antibody), and hydroxyproline assay (measure of total collagen content). A modified H&E grading system was used quantifying edema (0-3), inflammation (0-3), acinar necrosis (0-6), acinar atrophy (0-6), and hemorrhage (0-5). Sirius red was scored as follows:

Sirius red (1=normal, 2=moderate amts of interstitial collagen, 3=prominent collagen in periacinar and perivascular areas)

RESULTS:

     

H&E

   

sirius

hydroxy-

 

Edema

inflam

necros

acin atr

hemo

red

proline

Control

1 ± 0

0 ± 0

0 ± 0

0 ± 0

0 ± 0

1 ± 0

14.4 ± 1.3

24h

1.5 ± .3

1.3 ± .3*

.5 ± .5

0 ± 0

.3 ± .3

1 ± 0

13.5 ± 1.0

48h

2.8 ± .3*

2.8 ± .3*

2.8 ± .5*

2.3 ± .3*

1.8 ± 1.1

2 ± 0*

15.9 ± 2.5

72h

2.3 ± .3*

2.3 ± .3*

2 ± 0*

4.7 ± .7*

.3 ± .3

2.3 ± .3*

23.3 ± 1.4*

96h

2.8 ± .3*

2.5 ± .3*

2 ± 0*

6.0 ± 0*

.8 ± .8

3 ± 0*

34.6 ± 1.8

-results are expressed as mean ± SEM; *p < 0.05 compared to controls

Immunofluorescence microscopy demonstrated a progressive increase in collagen deposition in the periacinar spaces and loss of normal acinar architecture. Over 96 hr, SHOP was characterized by (1) acinar atrophy with appearance of duct-like complexes, (2) increased total pancreatic collagen, and (3) increased periacinar collagen deposition.

CONCLUSIONS: SHOP is a novel model of pancreatitis associated with edema and inflammation, but minimal necrosis and hemorrhage. Furthermore, SHOP is characterized by significant collagen deposition and acinar atrophy with replacement by duct-like complexes making it an ideal model to study the early cellular mechanisms of pancreatic fibrogenesis.

Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.

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