HYPERCHOLERESIS WITH CHOLATE INFUSION IN DOGS WITH PIGMENT GALLSTONES

We previously reported that dogs with pigment gallstones infused with taurocholate produce higher bile flow than normal dogs due to an incre ase in bile-acid independent bile flow. Since dogs with pigment gallst ones are taurine-depleted and secrete large amounts of unconjugated bi le salt, we hypothesized that the observed increased bile flow is seco ndary to the presence of unconjugated bile salts in the biliary tract, and cholate infusion was compared in normal and pigment gallstone dog s. Cholate increased bile flow significantly (P < 0.05) from 5.2 and 8 .2 to 31 and 57 mu l/kg/min in normal and pigment gallstones dogs, res pectively. Plots of bile flow Versus bile acid output yielded separate linear relationships with a higher slope in gallstone dogs, but manni tol clearance indicated that excess flow originated in the canaliculus . Extended cholate infusion (570 min) severely taurine depleted normal dogs and increased cholate secretion, but bile flow remained signific antly lower (P < 0.05) in normal dogs than in gallstone dogs. Choleret ic activity of cholate in normal dogs was similar to that of taurochol ate, but was nearly twice that of taurocholate in gallstone dogs. Chol eretic activity increased in both groups with extended cholate infusio n, suggesting adaptive changes in a biliary system bathed with unconju gated bile salts. These results are important since the increased bile flow in dogs with pigment gallstones would increase delivery of all b iliary components to the gallbladder contributing to the high concentr ations of gallbladder bile calcium previously observed in these dogs. It also has important physiological implications concerning the format ion of bile in the proximal biliary tree. The data are most consistent with either direct hepatocyte stimulation to secrete another anion or with cholate/anion exchange at the canalicular, rather than ductal, l evel.