Although gallbladder stasis exists in most patients with quence of it. [1][2][3][4][5] Identifying events in a chronological fashion is particularly difficult in humans before gallstone formation. 5 cholesterol gallstones, it is unknown whether stasis is a causative factor of gallstone disease or merely a consequence of Defective gallbladder emptying likely occurs before stone formation, followed by the appearance of cholesterol crysit. We studied the impact of sustained gallbladder stasis induced by a cholecystokinin (CCK)-A receptor antagonist (MK-tals. 1,6,7 In one report on patients with cholesterol crystals alone (without gallstones), gallbladder emptying was im-329) on gallstone formation in ground squirrels fed either a trace or a high-cholesterol diet. MK-329 markedly inhibited paired. 6 Unfortunately, all the patients in this study had chronic cholecystitis, a confounding factor, which in itself 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 õ .05) and could have adversely affected gallbladder motor function. 1,5,8 Ground squirrels fed a high-cholesterol diet form cholesincreased gallbladder fasting volume in vivo (control: 462 { 66 vs. MK-329: 1,004 { 121 mL; P õ .05). Whereas the terol crystals and/or gallstones within a reasonably short period. [9][10][11][12][13] Defective gallbladder contractility develops very high-cholesterol diet alone (1%-cholesterol diet / placebo) increased the cholesterol saturation index (CSI) in control early in these animals, concurrent with a rise in cholesterol saturation of bile and the appearance of cholesterol crystals, animals (trace-cholesterol diet / placebo), MK-329 significantly (P õ .05) decreased the CSI in both hepatic and gall-but before stone formation. A major limitation in this model is the inability to assess directly the primary role of gallbladbladder bile in animals on the trace-(trace-cholesterol diet / MK-329) as well as on the high-cholesterol diets (1%-choles-der hypomotility in the process of gallstone formation because of the concurrent changes in both hepatic bile formaterol diet / MK-329). The mucin content of the mucus layer on the epithelial surface of the gallbladder wall more than tion and gallbladder motility.13-14 Our previous study in the same animal model showed that a cholecystokinin (CCK)-A doubled (P õ .05) with the high-cholesterol diet; adding MK-329 to the latter group produced a further 82% increase (P receptor antagonist (MK-329) suppressed gallbladder emptying, but reduced the cholesterol saturation in both hepatic õ .05). The cholesterol diet / MK-329 group had the highest (100%) incidence of cholesterol crystals that were evident in and gallbladder bile.14 This apparent paradox challenges the traditional concept that gallbladder stasis is a primary fresh gallbladder bile, coincident with a shortened nucleation time (2.5 { 0.6 days; P õ .05 vs. the cholesterol diet / and/or contributing factor in cholesterol gallstone formation. [1][2][3][15][16][17][18] placebo ...