Abstracts
1997 Digestive Disease Week

Synergistic interactions between cholinergic mechanisms, cholecystokinin, and duct obstruction in acute pancreatitis pathogenesis.

I Samuel, RJ Joehl. Surgery, Northwestern Univ/VALMC, Chicago, IL.

Bile-pancreatic juice exclusion from gut exacerbates bile-pancreatic duct (BPD) obstruction-induced acute pancreatitis via cholinergic- and CCK-receptor mechanisms. Using acinar cell vacuolation and white blood cell infiltration as parameters of acinar cell injury, we studied effects of CCK and cholinergic agent carbachol (CCh)--individually and together--on rats with and without duct obstruction (n=5-9/group). Control Groups had 1) BPD dissection only (Sham), 2) BPD-ligation (duct obstruction with bile-pancreatic juice exclusion), or 3) BPD-ligation with duodenal bile-pancreatic juice replacement fresh from a donor rat (duct obstruction alone). Nonoperated-treated groups received 4) CCh 5µg/h s.c, 5) CCK 5µg/h s.c., or 6) both CCh and CCK. Operated-treated groups had BPD-ligation and bile-pancreatic juice replacement as in 3 above, and received 7) CCh, 8) CCK, or 9) both CCh and CCK. Rats were killed after 6 hrs. Hematoxylin-, eosin-stained sections of pancreas were examined in blinded fashion and scored based on degree of acinar cell vacuolation and white blood cell infiltration (range 0-5). RESULTS: (Mean±SEM, ANOVA, P<0.05) Acinar cell vacuolation and white blood cell infiltration associated with BPD-ligation were significantly ameliorated by bile-pancreatic juice replacement (3vs2). Acinar cell vacuolation was seen only with CCh+CCK, but not with either alone (6vs4/5). With duct obstruction, CCh resulted in acinar cell vacuolation and white blood cell infiltration (7vs4), while CCK resulted in white blood cell infiltration (8vs5). White blood cell infiltration after CCh+CCK was markedly greater with duct obstruction than without duct obstruction (9vs6). With duct obstruction, white blood cell infiltration after CCh+CCK was significantly greater than after either CCh or CCK (9vs7/8). [Figure not available.]

CONCLUSIONS: Concerning pathogenesis of acinar cell injury in this acute pancreatitis model : 1) A synergistic interaction exists between CCh and CCK. 2) Duct obstruction potentiates effects of CCh and CCK. 3) These findings indicate that CCK, cholinergic mechanisms, acinar hyperstimulation, and bile-pancreatic duct obstruction are involved in disease pathogenesis.