Two-barrier Model. If a tracer is transformed within the cells, or if its distribution is heterogeneous, two intracellular regions have to be considered, with a second barrier between them.
Model number: 0211
Lactate is a natural substrate of the liver. It is taken up by hepatocytes and is transformed to pyruvate by the action of the enzyme lactate dehydrogenase. The hydrogen atom bound to the central carbon atom of the molecule is transferred to NAD that is thus transformed to NADH. Various other dehydrogenases transfer this hydrogen to other metabolic intermediates who form a separate intracellular pool that can be assessed by the multiple indicator dilution method.
The following tracers were injected into the portal vein of an isolated buffer-perfused rat liver:
- [U14C]Urea (a tracer that is distrubuted rapidly within the perenchymal cells)
- L-[2-3H]lactate (CH3—C3HOH—COO–)
Enalaprilat, (S)-1-[N-[1-(carbonyl)-3-phenylpropyl-L-alanyl]-L-proline, is a drug metabolite formed by hydrolysis of the antihypertensive drug [[http://www.rxlist.com/cgi/generic/enalap.htm| enalapril]]. It is taken up by hepatocytes, where, because of its low water solubility, it is bound to intracellular proteins. This results an additional intracellular pool of protein-bound enalaprilat. Enalaprilat is excreted predominatly into the bile.
The following tracers were injected into the portal vein of a perfused rat liver:
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Schwab AJ (1984), Extension of the theory of the multiple indicator dilution technique to variable systems with an arbitrary number of rate constants. Math. Biosci. 71:57–79.
Schwab AJ, Barker F 3rd, Goresky CA, Pang KS (1990) Transfer of enalaprilat across rat liver cell membranes is barrier limited. Am J Physiol 258:G461-75.
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indicator dilution, barrier-limited, liver, transport, vascular volume, organ, Goresky transport tutorial, Data, PDE
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[This page was last modified 30Jul13, 10:13 am.]
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