Gallstones (GS) are a significant health problem with cholecystectomy the most common abdominal operation in many hospitals. In spite of a better understanding of cholesterol pigment glycoprotein complexes, biliary sludge and phospholipid metabolism, risk factors for most patients are not well defined. GS are more prevalent in females and are strongly associated with pregnancy. Obesity and older age also may be risks. Cholesterol (CHL) GS formation in experimental animals is associated with both bile lithogencity and abnormal biliary motility, but it is unclear whether stasis is an important primary event, contributing to the nucleation and growth of cholesterol crystals or simply a secondary phenomena from their presence. Patients with GS or pregnancy and animals with GA have gallbladder (GB stasis. Thus, the study of GB stasis and pregnancy are particularly relevant to our understanding of GS pathogenesis. Since GB function has pressure volume response as well as hierarchic and heuristic features in a complex neurohumoral arrangement, the potential mechanisms for abnormal biliary motility are legend. Our hypothesis is that GB stasis is a [primary defect in CHL GS formation. That biliary motility is altered before not as a consequence of cholelithiasis is supported by observations in pregnancy and experimental GS data. Since (1) GB stasis with increased cystic duct resistance (CDR) occurs early after initiating a lithogenic diet before crystals occur; (2) since increased GB prostaglandin (PG) synthesis are temporarily associated with these changes; (3) since PG may contribute to the regulation of smooth muscle contractions; and (4) since the sex steroids associated with pregnancy are known to influence GB PG synthesis and GB motility it follows that PG mediated GB stasis may play an important primary role in CHL GS formation. State of the art methodology for assessment of biliary motility (GB muscle strips and whole organ in vitro, GB emptying and CDR in situ, and cholescintigraphy or RISA in vivo) done while documenting bile lithogenicity, nucleation of CHL crystals and CHL GS formation in CHL feed prairies dog (PD) permits examination of both the magnitude and sequence of abnormal biliary motility during GS formation. Measurement of PG synthesis at critical points requires precise documentation of both GB stasis and crystal formation. With this model, the influence of gender, pseudopregnancy, the combination of pseudopregnancy and diet-induced hypersecretion of biliary CHL on biliary motility, GB PG synthesis and CHL GS formation can be assessed. With feeding and/or pseudopregnancy, the effects of pharmacologic and nonpharmacologic PG inhibitors on biliary motility and CHL GS help establish the role of PG in mediating GB stasis induce CHL GS formation. If abnormalities are, in fact, mediated by PG's, these studies could provide the potential for preventing CHL GS formation in individuals at high risk.
| Chapman, W C; Peterkin 3rd, G A; LaMorte, W W et al. (1989) Alterations in biliary motility correlate with increased gallbladder prostaglandin synthesis in early cholelithiasis in prairie dog. Dig Dis Sci 34:1420-4 |
