A decreased plasma clearance of sulphobromophthalein (BSP) is often observed during the latter half of normal human pregnancy (Tindall and Beazley 1965). It also occurs during the ingestion of oral contraceptives (Roman and Hecker 1968) and after treatment with oestrogens at doses similar to those produced daily in late pregnancy (Kappas 1968). A reduction in bile flow has been described after oestrogen treatment in rats (Javitt and Harkavy 1969;Forker 1969;Kreek et al. 1967), but no attempts appear to have been made to associate changes in bile flow rate with alterations in BSP excretion.In this study, the effect of variations in the flow of bile on the excretion of BSP was assessed in pregnant and non-pregnant rabbits.
Materials and MethodsSeven 4-month-old New Zealand white rabbits weighing 2·7-3· S kg were obtained at the time of nesting, which was within 2-3 days of term. Fourteen virgin rabbits of the same age and weight acted as controls. Experiments were conducted alternately with pregnant rabbits and controls and both groups of animals were fasted for at least IS hr before operation.Rabbits were anaesthetized with pentobarbitone sodium (i.v. 25 mg/kg body weight). In each rabbit, the cystic duct was ligated and a polyethylene catheter (1·50 mm o.d.), 15 cm in length, was inserted into the common bile duct at the hilus of the liver. Initial rates of bile flow were determined for both pregnant and control rabbits immediately after cannulation. Sulphobromophthalein (Bromthalein, E. Merck, Darmstadt, Germany; 50 mg/ml) was injected into the marginal ear vein at the dose of O· 75, 2· 0, and 5·0 mg/kg in non.pregnant rabbits and 2·0 and 5·0 mg/kg in pregnant rabbits, and sequential samples of bile were collected into tared containers until the samples were free from the dye. Each rabbit was used for up to three separate determinations of BSP excretion rate. In order to estimate the excretion rate of BSP at low rates of bile flow in control rabbits, bile was allowed to drain from all control rabbits for a period of 4 hr. After this time, bile flow rate had declined significantly due to interruption of the enterohepatic circulation of bile salts.The concentrations and excretion rates of BSP were estimated after dilution of O· 07 -ml portions of bile with 3 ml of O·OSN NaOH; this achieved concentrations of BSP that could be measured at 585 nm in a Beckman DU 4700 spectrophotometer. Since the excretory rates of BSP into bile increased to a peak about 12 min after injection, then gradually decreased with time, the excretory rate for a particular dose of dye was taken arbitrarily as the product of bile * Manuscript