Kinetics of hepatic transport of 4-methylumbelliferone in rats. Analysis by multiple indicator dilution method

1987 ◽  
Vol 15 (1) ◽  
pp. 25-38 ◽  
Author(s):  
Seiji Miyauchi ◽  
Yuichi Sugiyama ◽  
Yasufumi Sawada ◽  
Kaname Morita ◽  
Tatsuji Iga ◽  
...  
1982 ◽  
Vol 243 (1) ◽  
pp. G76-G89
Author(s):  
B. A. Luxon ◽  
E. L. Forker

The "multiple-indicator dilution method" of measuring hepatic transport kinetics is subjected to simulation analysis. The objective is to examine the errors that may arise from treating the nonexchanging vasculature as a simple delay and to study the information content of simulated venous outflow curves. We find that the method cannot be counted on to provide consistently reliable estimates of either the transport rate constants or the sinusoidal volume. Estimates of the rate constant for irreversible solute removal from within liver cells are especially likely to be wrong. We suggest an alternative formulation of the governing differential equations that can substantially improve the estimates of the uptake parameter. These estimates may otherwise be subject to large systematic errors. Finally we discuss why the steady-state extraction fraction computed from the fitted parameters should be checked against a model-independent estimate obtained directly from the areas under the outflow curves. A method for making this comparison is at hand and should prove useful as a minimum criterion of internal consistency in animal experiments.


1999 ◽  
Vol 86 (6) ◽  
pp. 1866-1880 ◽  
Author(s):  
D. L. Roerig ◽  
S. H. Audi ◽  
J. H. Linehan ◽  
G. S. Krenz ◽  
S. B. Ahlf ◽  
...  

We evaluated the potential utility of a group of indicators, each of which targets a particular tissue property, as indicators in the multiple-indicator dilution method to detect and to identify abnormalities in lung tissue properties resulting from lung injury models. We measured the pulmonary venous outflow concentration vs. time curves of [14C]diazepam, 3HOH, [14C]phenylethylamine, and a vascular reference indicator following their bolus injection into the pulmonary artery of isolated perfused rabbit lungs under different experimental conditions, resulting in changes in the lung tissue composition. The conditions included granulomatous inflammation, induced by the intravenous injection of complete Freund’s adjuvant (CFA), and intratracheal fluid instillation, each of which resulted in similar increases in lung wet weight. Each of these conditions resulted in a unique pattern among the concentration vs. time outflow curves of the indicators studied. The patterns were quantified by using mathematical models describing the pulmonary disposition of each of the indicators studied. A unique model parameter vector was obtained for each condition, demonstrating the ability to detect and to identify changes in lung tissue properties by using the appropriate group of indicators in the multiple-indicator dilution method. One change that was particularly interesting was a CFA-induced change in the disposition of diazepam, suggestive of a substantial increase in peripheral-type benzodiazepine receptors in the inflamed lungs.


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