THE DISTRIBUTION AND EXCRETION OF S35-LABELED SULFO-BROMOPHTHALEIN-SODIUM ADMINISTERED TO DOGS BY CONTINUOUS INFUSION 1
Authors: R. W. Brauer, R. L. Pessotti, J. S. Krebs
Journal: Journal of Clinical Investigation (1955)

It has been known for some time that continuous tent, upon assumptions regarding the storage of intravenous infusion of sulfo-bromophthalein-so-the dye in tissues supplied by the splanchnic ir- dium (referred to below as BSP) in dogs as well culation; second, BSP is a most useful prototype as in man results eventually in a steady state in substance for theoretical studies of bile formation which blood and bile concentrations, and usually and bile secretion, and knowledge of its actual the rate of biliary excretion of the dye, remain sites of deposition is essential if serious errors of constant (1).Bradley and co-workers have interpretation are to be avoided in this connection.pointed out that such a steady state can only beThe preparation of S'5-labeled BSP (6) pro- achieved at infusion rates resulting in blood vides a tool which permits a direct approach to levels of BSP lower than a certain liminal value these questions.The present communication (20 mg. per L. in man [2] or 40 mg.per L. ac-deals with the application of S"5-labeled BSP to cording to other workers [3]).The present au-the study of the distribution of BSP when ad- thors (4) have pointed out in a previous communi-ministered to dogs by continuous intravenous cation that during such steady state conditions, infusion.the rate of biliary excretion of the dye is con- sistently below the rate of infusion, indicating that MATERIALS AND METHODS considerable amounts of sulfo-bromophthalein-so-Mongrel dogs under sodium pentobarbital anesthesia dium are being stored in the body.Thi-s is in ac-Were studied after cholecystectomy and preparation of cord with observations by Cantarow and Wirts common bile duct fistulac.When desired, liver injury (5) who showed that, following the administration was induced by means of CCIL administered by stomach of single doses of sulfo-bromophthalein-sodium, tube (0.5 cc. per Kg., 72 and again 24 hours before opera- dye excretion into bile lagged by a considerable tion).BSP' was administered intravenously by means of time behind the disappearance of most of a continuous infusion pump.For details of animal pftherody from the blood stream; they concluded selection and maintenance, of induction of liver injury of the dye from the blood stream; they concluded and surgery see (4). that this period must represent storage of the dye. S'-labeled BSP was prepared by sulfonation of tetra-The actual sites of storage of this "lost BSP" bromphenolphthalein and purification of the product by could not be determined with certainty in either chromatography and recrystallization (6).Coloritnetric of these investigations; indications were obtained analyses for BSP were undertaken in the cases of the Of these investigations; indications were obtained blood and bile samples only.The procedure employed, that a considerable amount of dye is retained in a modification of that described in (7), cf. also (8), con- the liver prior to excretion.Further investigation sisted of diluting the samples with water, then acetone, in of this point seemed indicated for two reasons: such fashion as to attain final protein concentrations be- First, application of BSP to clinical studies of tween 0.8 and 12 per cent, and acetone concentrations of 60 per cent by volume.Blood plasma samples were hepatic blood flow depend, to a considerable ex-then stored in the refrigerator for one hour and the pro- 1 This work was carried out under contract no.AT-tein precipitate removed by centrifugation; bile samples (40-1)-230 between the Atomic Energy Commission and could be used without such intermediate treatment.Louisiana State University, and under Research ~Aliquots of the solutions were collected, 0.1 cc.