Exacerbation of acute pancreatitis by combined cholinergic stimulation and duct obstruction.
BACKGROUND
The role of cholinergic pathways in the pathogenesis of bile-pancreatic duct ligation (BPDL)-induced acute pancreatitis in rats remains controversial. We hypothesized that cholinergic stimulation exacerbates acute pancreatic inflammation in the presence of duct obstruction.


METHODS
We studied 34 rats divided into 5 groups as follows: (1) sham operation; (2) BPDL; (3) BPDL with duodenal bile-pancreatic juice (BPJ) replacement fresh from a donor rat; (4) BPDL with BPJ replacement as in 3 above, and carbachol (CCh) 5 ug/h subcutaneously; or (5) CCh 5 ug/h subcutaneously only. Rats were killed after 6 hours.


RESULTS
The P value was less than .05 by analysis of variance. Pancreatic morphologic changes and zymogen fraction hyperamylasemia seen with duct ligation (2 vs. 1) were ameliorated significantly by duodenal BPJ replacement (3 vs. 2), but not when exogenous CCh was administered (4 vs. 3), whereas CCh alone showed no significant changes compared with sham (5 vs. 1).


CONCLUSIONS
Cholinergic stimulation and duct obstruction synergistically amplify acinar hyperstimulation and exacerbate acute pancreatitis.
Samuel
Isaac
I
Department of Surgery, Veterans Affairs Medical Center, Iowa City, IA, USA. isaac-samuel@uiowa.edu
Chaudhary
Ashok
A
Fisher
Rory A
RA
Joehl
Raymond J
RJ
D000818:Animals; D017734:Bile Ducts, Extrahepatic / Q000601:surgery*; D002217:Carbachol / Q000494:pharmacology*; D001651:Cholestasis, Extrahepatic / Q000150:complications*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004195:Disease Models, Animal; D008026:Ligation / Q000009:adverse effects; D008297:Male; D046790:Pancreas, Exocrine / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D000516:alpha-Amylases / Q000378:metabolism
D018679:Cholinergic Agonists; D002217:Carbachol; D000516:alpha-Amylases