Defective Gallbladder Contractility Associated with Increased Bile Lithogenicity in Ground Squirrels and Prairie Dogs

Summary

Richardson ground squirrels were fed on either a trace cholesterol (control) diet or a 1% w/w cholesterol (test) diet. The lithogenic index of the gallbladder bile increased on the test diet from 0.52±0.03 to 0.81±0.04 (p<0.0001). The isometric tensions generated in vitro by cholecystokinin octapeptide (CCK₈), acetylcholine (Ach) and depolarization by 70 mM K⁺ solutions were significantly reduced by 50% though there was no shift in the normalized dose-response curve. In those animals which proceeded to the stage of cholesterol stone formation the defect in gallbladder contractility became even more severe. Ileal muscle from test animals showed no loss of contractility in response to any of the three stimuli. A similar defect occurred in prairie dogs associated with increased lithogenicity.

Thus, in these animal models, there is a clear and apparently specific defect in gallbladder contractility which onsets with early changes in bile lithogenicity and becomes progressively worse as cholesterol stones develop. This defect would contribute to gallbladder stasis which, in turn, might be a significant factor in the eventual formation of cholesterol gallstones.