Impaired Gallbladder Emptying Before Gallstone Formation in the Prairie Dog

Abstract

Several human and experimental observations suggest that gallbladder stasis is an important link between the hepatic secretion of cholesterol saturated bile and the formation of cholesterol gallstones. In the cholesterol-fed prairie dog model, gallbladder stasis occurs before gallstone formation. In this study we sought to determine the specific defects in extrahepatic biliary physiology responsible for gallbladder stasis in this model. Adult male prairie dogs were fed either a trace cholesterol or a 0.4% cholesterol-enriched diet. In acute terminal experiments, gallbladder contents were examined for cholesterol crystals and gallstones, and gallbladder function was determined at rest and in response to intravenous cholecystokinin-octapeptide. The following alterations in gallbladder function developed concurrently with biliary cholesterol crystallization, but before gallstone formation: (a) decreased gallbladder emptying, (b) increased intragallbladder pressure in response to cholecystokinin-octapeptide, (c) increased cystic duct closing pressure, and (d) increased resistance to outflow through the cystic duct.