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Sustained gallbladder stasis promotes cholesterol gallstone formation in the ground squirrel
Author(s) -
Xu Q,
Mantle M,
Pauletzki J G,
Shaffer E A
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510260404
Subject(s) - cholesterol , gallbladder , medicine , gallstones , endocrinology , prairie dog , gastroenterology , cholecystokinin , biology , receptor , ecology
Although gallbladder stasis exists in most patients with cholesterol gallstones, it is unknown whether stasis is a causative factor of gallstone disease or merely a consequence of it. We studied the impact of sustained gallbladder stasis induced by a cholecystokinin (CCK)‐A receptor antagonist (MK‐329) on gallstone formation in ground squirrels fed either a trace or a high‐cholesterol diet. MK‐329 markedly inhibited gallbladder contraction in vitro in response to CCK (at EC 100 , control: 3.6 ± 0.5 vs. MK‐329: 1.1 ± 0.3 g; P < .05) and increased gallbladder fasting volume in vivo (control: 462 ± 66 vs. MK‐329: 1,004 ± 121 µL P < .05). Whereas the high‐cholesterol diet alone (1%‐cholesterol diet + placebo) increased the cholesterol saturation index (CSI) in control animals (trace‐cholesterol diet + placebo), MK‐329 significantly ( P < .05) decreased the CSI in both hepatic and gallbladder bile in animals on the trace‐(trace‐cholesterol diet + MK‐329) as well as on the high‐cholesterol diets (1%‐cholesterol diet + MK‐329). The mucin content of the mucus layer on the epithelial surface of the gallbladder wall more than doubled ( P < .05) with the high‐cholesterol diet; adding MK‐329 to the latter group produced a further 82% increase ( P < .05). The cholesterol diet + MK‐329 group had the highest (100%) incidence of cholesterol crystals that were evident in fresh gallbladder bile, coincident with a shortened nucleation time (2.5 ± 0.6 days; P < .05 vs. the cholesterol diet + placebo group, 5.8 ± 1.0 days or the other 2 groups, >21 days). Bile from animals on the trace‐cholesterol diet, whether or not receiving MK‐329, lacked crystals in bile and exhibited a normal nucleation time (>21 days). Thus, stasis per se may lower the CSI, but its detrimental effect on the gallbladder predominates locally, and so accelerates cholesterol crystal formation in this model.