Slow intestinal transit: A motor disorder contributing to cholesterol gallstone formation in the ground squirrel

✍ Scribed by Q Xu; R B Scott; D T Tan; E A Shaffer

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 251 KB
• Volume: 23
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510230650

✦ Synopsis

Impaired gallbladder motility is an established factor stone disease may initially represent a metabolic liver in cholesterol gallstone formation. We assessed whether disorder but can be modulated by the enterohepatic altered small intestinal smooth muscle contractility with circulation of bile salts. 2,[9][10][11][12][13][14] The gallbladder (by filling slow transit might potentiate gallstone formation by furand emptying) and the small intestine (by governing ther impeding enterohepatic cycling of bile acids. transit time) are the rate-limiting steps that control Ground squirrels were fed a 1% or a trace (controls) chothe enterohepatic cycling frequency of bile salts and lesterol diet. Small intestinal transit was evaluated from their flux through the liver. [9][10]14,15 Enterohepatic cy-51 Cr distribution in conscious, fasted animals 20 minutes cling thus has a profound impact on biliary lipid compoafter infusion into the proximal jejunum. Small intestisition and bile salt pool size, as demonstrated in panal and gallbladder smooth muscle contractility was detients with gallstones and confirmed in animal models termined in vitro. Biliary lipid secretion was measured from the cannulated common duct and the bile salt pool of cholesterol gallstone formation. 2,6,[9][10][11][12][13][14] size calculated by isotope dilution. Gas-liquid chroma-Prolonged small intestinal transit, like impaired tography (GLC) assessed bile salt profile. In animals on gallbladder emptying, should hinder enterohepatic cythe 1% cholesterol diet, aboral transit was significantly cling and lower the bile salt secretion rate, thus predisdelayed, the maximal contractile response to bethaposing to the formation of gallbladder bile saturated nechol was markedly increased (P õ .05) with no change with cholesterol. 9,10,14 Recent studies of cholesterol gallin median effective concentration in either circular or stone pathogenesis in nonobese subjects and in acromelongitudinal muscle strips from both the jejunum and galic patients treated with the long-acting somatoileum, and the gallbladder contractile responses to bethanechol and cholecystokinin (CCK) were decreased. statin analog, octreotide, support and advance this Cholesterol saturation index and the fraction of deoxyhypothesis. In each condition, either prolonged wholecholic acid in the pool doubled, whereas the total bile gut transit or lengthened small intestinal transit has salt pool size remained unchanged in cholesterol-fed anbeen linked to an increased production of deoxycholate, imals. In this model, a high-cholesterol diet is associated saturated gallbladder bile, and the subsequent formawith altered small intestinal smooth muscle contractility tion of cholesterol gallstones. [16][17][18] The importance of the and prolonged small intestinal transit, in addition to dicontribution of small intestinal transit time has not minished gallbladder contractility. The resulting slugyet been clarified because previous measurements of gish enterohepatic cycling of bile salts, associated with expanded deoxycholate pool, contributes to cholesterol intestinal transit have included gastric emptying as a gallstone formation. (HEPATOLOGY 1996;23:1664-1672.) component. [16][17][18] Prolonged intestinal transit might be an intrinsic part of cholesterol gallstone disease, akin to the gallbladder motility disorder. Furthermore, The pathogenesis of cholesterol gallstone disease is slowed transit through the distal ileum (and the colon) multifactorial, involving disturbances in biliary lipid may lead to increased production of deoxycholate, secretion, cholesterol crystal nucleation, and gallbladwhich in itself can slow down small intestinal transit. 19 der motility. [1][2][3][4][5][6][7][8] The secretory defect in cholesterol gall-It is therefore appropriate to evaluate small intestinal transit and smooth muscle contractility directly in a defined animal model and clarify the findings reported Abbreviations: CCK, cholecystokinin; GLC, Gas-liquid chromatography; in humans.

CSI, cholesterol saturation index.

The ground squirrel, when fed a high-cholesterol