Role of the hepatic artery in the metabolism of phenacetin and acetaminophen: An intravital microscopic and multiple-indicator dilution study in perfused rat liver

Hepatology ◽  
1994 ◽  
Vol 20 (3) ◽  
pp. 672-683
Author(s):  
K. Sandy Pang ◽  
Igor A. Sherman ◽  
Andreas J. Schwab ◽  
Wanping Geng ◽  
Ford Barker ◽  
...  
Keyword(s):  
Hepatic Artery ◽  
Rat Liver ◽  
Indicator Dilution ◽  
Perfused Rat Liver ◽  
Multiple Indicator Dilution ◽  
Multiple Indicator

Hepatic uptake of hippurate: a multiple-indicator dilution, perfused rat liver study

1998 ◽  
Vol 274 (1) ◽  
pp. G10-G20 ◽  
Author(s):  
Tsutomu Yoshimura ◽  
Andreas J. Schwab ◽  
Lei Tao ◽  
Ford Barker ◽  
K. Sandy Pang
Keyword(s):  
Benzoic Acid ◽  
Rat Liver ◽  
Hepatic Uptake ◽  
Indicator Dilution ◽  
Monocarboxylate Transporter ◽  
Maximal Velocity ◽  
Perfused Rat Liver ◽  
Hepatic Transport ◽  
Multiple Indicator Dilution ◽  
Multiple Indicator

The hepatic transport of hippuric acid (HA), a glycine-conjugated metabolite of benzoic acid that exhibits only modest plasma albumin binding (binding association constant of 2.1 × 103M−1), was studied in the single-pass perfused rat liver (12 ml/min), using the multiple indicator dilution (MID) technique. The venous recovery of [3H]HA on portal venous injection of a MID dose containing a mixture of a set of noneliminated reference indicators and [3H]HA revealed a survival fraction of unity, corroborating the lack of disappearance of bulk HA from plasma. When the outflow recovery was fitted to the barrier-limited model of Goresky et al. (C. A. Goresky, G. G. Bach, and B. E. Nadeau. J. Clin. Invest. 52: 991–1009, 1973), the derived influx ( P in S ) and efflux ( P out S ) permeability-surface area products were found to be dependent on the concentration of HA (1–930 μM); P in S and P out S were ∼3.5 times the plasma flow rate at low HA concentration, but decreased with increasing HA concentration. All values, however, greatly exceeded the expected contribution from passive diffusion, because the equilibrium distribution ratio of chloroform to buffer for HA was extremely low (0.0001 at pH 7.4). The tissue equilibrium partition coefficient ( P in/ P out, or ratio of influx to efflux rate constants, k 1/ k −1) was less than unity and decreased with concentration. The optimized apparent Michaelis-Menten constant and maximal velocity were 182 ± 60 μM and 12 ± 4 nmol ⋅ s−1 ⋅ g−1, respectively, for influx and 390 ± 190 μM and 29 ± 13 nmol ⋅ s−1 ⋅ g−1, respectively, for efflux. In the presence ofl-lactate (20 mM), however, P in S for the uptake of HA (174 ± 3 μM) was reduced. Benzoic acid (10–873 μM) was also effective in reducing hepatic uptake of HA (5.3 ± 0.9 μM). These interactions suggest that MCT2, the monocarboxylate transporter that mediates the hepatic uptake of lactate and other monocarboxylic acids, may be involved in HA transport.

Carrier-mediated uptake and excretion of bromosulfophthalein-glutathione in perfused rat liver: A multiple indicator dilution study

Hepatology ◽  
1995 ◽  
Vol 22 (4) ◽  
pp. 1188-1207 ◽  
Author(s):  
Wan Ping Geng ◽  
Andreas J. Schwab ◽  
Carl A. Goresky ◽  
K. Sandy Pang
Keyword(s):  
Rat Liver ◽  
Indicator Dilution ◽  
Perfused Rat Liver ◽  
Multiple Indicator Dilution ◽  
Multiple Indicator

Salicylamide sulfate cell entry in perfused rat liver: A multiple-indicator dilution study

Hepatology ◽  
1994 ◽  
Vol 19 (1) ◽  
pp. 229-244 ◽  
Author(s):  
Xin Xu ◽  
Andreas J. Schwab ◽  
Ford Barker Iii ◽  
Carl A. Goresky ◽  
K. Sandy Pang
Keyword(s):  
Rat Liver ◽  
Indicator Dilution ◽  
Cell Entry ◽  
Perfused Rat Liver ◽  
Multiple Indicator Dilution ◽  
Multiple Indicator

Characterization of calcium deprivation-induced cholestasis in the perfused rat liver

1985 ◽  
Vol 249 (1) ◽  
pp. G48-G57 ◽  
Author(s):  
J. Reichen ◽  
F. Berr ◽  
M. Le ◽  
G. H. Warren
Keyword(s):  
Rat Liver ◽  
Bile Flow ◽  
Tritiated Water ◽  
Isolated Hepatocytes ◽  
Indicator Dilution ◽  
Perfused Rat Liver ◽  
Dilution Technique ◽  
Multiple Indicator Dilution ◽  
Indicator Dilution Technique ◽  
Multiple Indicator

To elucidate the role of calcium in regulation of canalicular bile flow, we studied biliary sucrose permeability and the transport kinetics of taurocholate in the in situ perfused rat liver. Calcium deprivation did not adversely affect viability or ultrastructural appearances of the liver. Removal of calcium led to initial choleresis followed by cholestasis dependent on external ionized calcium concentration. Biliary recovery of [14C]sucrose relative to that of tritiated water was determined by a biliary multiple-indicator dilution technique. Analysis in terms of irreversible thermodynamics suggested that biliary permeability to sucrose increased due to a change in the sieving coefficient from 0.135 to 0.435. Biliary recovery of taurocholate was significantly (P less than 0.001) reduced in low-calcium medium (from 79.6 +/- 6.5 to 17.6 +/- 11.8%). This was not due to a defect in hepatocellular uptake of taurocholate as determined in the perfused rat liver by a multiple-indicator dilution technique and in isolated hepatocytes. We conclude that calcium deprivation-induced cholestasis is characterized by an increased biliary permeability, a defect in cellular translocation and/or canalicular secretion of bile salts, and a defect in bile salt-independent bile flow.

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