The formation of gallstones in the cholesterol-fed guinea pig may be preceded by the orderly appearance of a series of functional abnormalities in the biliary tract which contribute to the pathogenesis of gallstones in this model. Although a variety of abnormalities are known to be associated with stone formation, their occurrence in relation to the stages of cholelithiasis and their relative importance in pathogenesis are obscure.
The specific aims are: I. To document the stages of gallstone formation in the guinea pig by examining gallbladder and hepatic bile for a) alterations in relative lipid concentration, b) microscopic crystals by polarizing microscopy, c) macroscopic stones, and d) histologic or bacteriologic evidence of inflammation and/or infection. Animals on a control diet or a cholesterol-supplemented diet for periods of 1,3; 6 or 12 weeks will be examined. II. To temporally correlate the appearance of biliary functional abnormalities with the stages of gallstone formation. The following parameters will be measured during a control or cholesterol-supplemented diet at intervals of 1, 3, 6 and 12 weeks: 1) Relative lipid composition of gallbladder and hepatic bile using standard assays. 2) Gallbladder volume will be measured by displacement and by aspiration of contents. Absorption will be calculated by measuring transmural weight loss of a physiologic salt solution. Hepatic secretion will be measured by collecting the hepatic outflow for 1 hour. 3) Meal-stimulated gallbladder emptying will be assessed by comparing the 30 minute post-prandial gallbladder volume with fasting volume in similar animals. 4) Gallbladder contractile response to octapeptide cholecystokinin will be assessed by measuring tension changes in gallbladder strips or by measuring pressure changes of the whole gallbladder in-vitro. 5) Total glycoprotein content of gallbladder and hepatic bile will be measured by PAS reaction. 6) The rate of endogenous prostaglandin synthesis gallbladder strips will be measured in-vitro with RIA. III. To assess the effects of aspirin and indomethacin therapy on these parameters and on stone formation.
| LaMorte, W W; LaMont, J T; Hale, W et al. (1986) Gallbladder prostaglandins and lysophospholipids as mediators of mucin secretion during cholelithiasis. Am J Physiol 251:G701-9 |
| LaMorte, W W; Booker, M L; Scott, T E et al. (1985) Increases in gallbladder prostaglandin synthesis before the formation of cholesterol gallstones. Surgery 98:445-51 |
