Metabolism of Halothane as a Function of Substrate Concentration in the Isolated Perfused Rat Liver Preparation

Author(s):  
I. Rösch ◽  
E. Dallmeier
1987 ◽  
Vol 167 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Allan W. Wolkoff ◽  
Kirsten L. Johansen ◽  
Tobias Goeser

2021 ◽  
Author(s):  
Marco Stebel ◽  
Nevenka Medic ◽  
Paola Pelizzo ◽  
Paola Sist ◽  
Federica Tramer ◽  
...  

Abstract We present a protocol for the study of bilirubin uptake in the isolated and perfused rat liver. The liver is perfused with an albumin-free saline buffered solution supplemented with glucose, pyruvate and lactate, in the absence of oxygen, at a physiologically low flow rate. Fractions of the venous effluent are collected and analyzed for bilirubin, bilirubin glucuronide and biomarkers of liver integrity. The liver preparation is viable and intact for 1 h after isolation from the general circulation, with constant levels of both bilirubin and bilirubin glucuronide (< 2 nM) in the effluent. Up to 12 boli of 10 nmol bilirubin can be sequentially injected into the portal vein without and with molecules that target sinusoidal membrane transporters of organic anions. Selective inhibition of bilirubin or bilirubin glucuronide uptake is detected as transient peaks in the effluent (Cmax up 6 to 60 nM). This protocol allows collecting repeated observations in the same liver, thus reducing the animal number by a factor of 10.


1974 ◽  
Vol 52 (3) ◽  
pp. 441-450 ◽  
Author(s):  
Mervin Moldowan ◽  
G. D. Bellward

An analytical procedure for the measurement of 14C-imipramine and its metabolites in liver, bile, and perfusion fluid has been studied using the isolated perfused rat liver technique. The extraction efficiency and specificity have been found to be high (efficiency with liver perfusion, 90–100%; specificities: imipramine, 96.6%; desmethylimipramine, 96.7%; imipramine-N-oxide, 90%). The hydroxylation of imipramine was close to the maximal rate at a substrate concentration of 0.5 × 10−4 M (15 min perfusion). The demethylation reaction reached a maximal rate at an estimated substrate concentration of 1.25 × 10−4 M. The formation of the N-oxide metabolite remained linear at 2 × 10−4 M imipramine. It was found that the half-life of imipramine in the perfusion fluid was not an accurate method of estimating imipramine metabolism as a result of a change in distribution. Exogenous desmethylimipramine inhibited the hydroxylation reaction; inhibition of demethylation required higher concentrations.


1993 ◽  
Vol 45 (3) ◽  
pp. 763-765 ◽  
Author(s):  
Susan L. Elliott ◽  
Denis J. Morgan ◽  
Peter W. Angus ◽  
Hany Ghabrial ◽  
Richard A. Smallwood

1987 ◽  
Vol 36 (13) ◽  
pp. 2238-2239 ◽  
Author(s):  
Stephen A. Ward ◽  
George W. Mihaly ◽  
Deborah D. Nicholl ◽  
Alasdair M. Breckenridge ◽  
Geoffrey Edwards

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