Hepatic Storage and Excretion of Sulfobromophthalein Sodium in the Dog *

Abstract

The use of a halogenated phthalein dye for the investigation of hepatic function was first proposed by Rowntree, Hurwitz and Bloomfield (1) in 1913. Their technique required the measurement of the fecal excretion of phenoltetrachlorphthalein following its parenteral administration. However, it was subsequently shown by Rosenthal and White (2) that intravenously administered phenoltetrabromophthalein disulfonate (BSP) is removed from the blood almost exclusively by the liver and that the function of the liver may therefore be evaluated by measuring the rate of disappearance of this dye from the plasma.Various lines of evidence support the view that the removal of BSP (and presumably many other substances) from the plasma involves two processes: 1) storage of the material in the liver and 2) biliary excretion. Following the intravenous administration of BSP to dogs it was first shown by Wirts and Cantarow (3) that the output of BSP in the bile continues for over three hours after its virtual disappearance from the plasma, indicating that this material is first taken up by the liver and then gradually excreted. This observation was confirmed by Brauer and Pessotti (4), also in dogs. The existence of a similar hepatic BSP storage mechanism in man is evident from the studies of Mendeloff, Kramer, Ingelfinger and Bradley (5) in which a retardation of the BSP disappearance rate from plasma was noted when successive identical intravenous dosts were administered 30 minutes apart.

Biliary Transport and Hepatic Storage of Sulfo-Bromophthalein Sodium in the Unanesthetized Dog, in Normal Man, and in Patients With Hepatic Disease *

“…The magnitude of the average estimated Tm in dogs (1.9 mg per minute per 10 kg) is consistent with previous observations in this laboratory (9,10), but is considerably lower than the Lm of 4.4 mg per minute per 10 kg estimated by Mason, Hawley and Smith (11). A possible explanation for this difference is that Mason and co-workers employed a correction for variation in plasma concentration which did not take the storage phenomenon into account.…”

“…In the case of another phthalein dye, I131-labeled rose bengal, an accumulation or "storage phase" is apparent in the curves obtained by external counting over the liver after intravenous injection (7), and high concentration within liver cells has been confirmed by radioautography (8). Although it has been suggested that accumulation of BSP may proceed until there is complete "saturation" of intrahepatic storage sites (4,9), more recent evidence indicates that the process tends toward an equilibrium state in which the quantity (and hence the concentration) of BSP in the liver is directly proportional to the concentration of dye in the surrounding plasma (10) storage capacity" (S) as the number of milligrams of BSP stored in the liver per milligram per 100 ml of plasma concentration. The value of S can be estimated by comparison of the rates of movement of BSP into the liver associated with different rates of change of plasma concentration (10).…”

“…There is convincing indirect evidence in the dog (9)(10)(11), in the rabbit (12,13), and in man (14,15) that the secretion of BSP into the bile is limited by a definite maximal rate, analogous to the transport maximum, or "Tm," which is demonstrable for many substances secreted by the renal tubules. For understandable technical reasons the BSP transport maximum has not, until the present, been measured directly by bile collection.…”

“…Moreover, because of the nature of the BSP storage process, the rate of biliary secretion cannot be equated to the rate of hepatic removal of BSP from the plasma unless the plasma level is absolutely constant. An indirect estimation of the BSP transport maximum is possible, nevertheless, by analysis of the data obtained during determination of relative storage capacity (10).…”

The Biliary Excretion of Sulfbromophthalein in the Pig

“…The characteristics of the hepatic uptake and biliary excretion of Sulfbromophthalein (BSP) have been previously reported in man (Wheeler, Meltzer and Bradley, 1960;Barber-Riley, Goetzee, Richards and Thomson, 1961) and for a number of laboratory species including the dog (Brauer and Pessotti, 1950;Wheeler, Epstein, Robinson and Snell, 1960), the sheep (Gronwall and Cornelius, 1970;Tucker, Mitchell and Little, 1971), the rat (Klaassen and Plaa, 1967), and the rabbit (Lewis, 1950). However, similar data are not available for the pig; what previous studies there are have given incomplete data on serum clearance in the intact animal (Cysewski, Pier, Engstrom, Richard, Dougherty and Thurston, 1968;Baker, Cushieri and Hanson, 1974) or have been concerned with BSP handling by the isolated perfused pig liver (Ham, Pirola and Elmslie, 1969).…”