Hepatic storage and biliary transport maximum of taurocholate and taurochenodeoxycholate in the dog

The purpose of this work was to validate for taurocholate and taurochenodeoxycholate the multiple infusion method of Wheeler et al. previously used for the study of hepatic sulphobromophthalein transport and to obtain numerical estimates of the relative storage capacity and secretory transport maximum of both bile acids. Experiments were performed in anaesthetized dogs after depletion of the endogenous bile acid pool. Bile was collected continuously to prevent recirculation of bile acids and to measure their secretion rates. Taurocholate or taurochenodeoxycholate were infused intravenously at 3 different rates and blood samples were collected every ten min to measure serum bile acid concentrations. Extrahepatic distribution spaces of taurocholate and taurochenodeoxycholate were measured by an isotope dilution method. Serum bile acid concentrations varied linearly with time during the last 30 min of each infusion period. A linear relationship was found between the calculated hepatic removal rate and the rate of change of serum bile acid concentration. The mean values of relative storage capacity were (in mumol.mumol-1.l-1.kg body weight-1) 0.16 +/- SD 0.07 for taurocholate and 0.08 +/- SD 0.03 for taurochenodeoxycholate. The mean values for secretory transport maximum were (in mumol.min-1.kg body weight-1) 4.81 +/- SD 1.24 for taurocholate and 3.56 +/- SD 0.60 for taurochenodeoxycholate. The values of secretory transport maximum with the multiple infusion method were only slightly higher than those obtained by direct measurement of biliary secretion. The values of relative storage capacity obtained during infusions resulting in decreasing plasma concentrations were usually lower than those obtained when the plasma concentration increased. This suggests that the limitations of the method previously noted for sulphobromophthalein may apply to bile acids.