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Identification and Modeling of Parameters that Influence Microdialysis Sampling in vitro and in vivo
Stenken, Julie Ann
Stenken, Julie Ann
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Abstract
Microdialysis sampling has matured into a standard technique for sampling the
rat brain in vivo. Microdialysis is beginning to be used for sampling from other
tissues in laboratory animals. It has also been used in humans. The amount of
material that enters or leaves a microdialysis probe is dependent upon many factors,
some of which are presented in this dissertation. These factors include forced
convection around the dialysis membrane, hindered diffusion through the membrane,
and kinetic processes that occur in the tissue space. The aims of these studies were
to identify factors that affect extraction efficiency in microdialysis systems and to
develop develop methods to quantitate these factors.
By setting up a specialized flow apparatus the effects of forced convection
around a microdialysis membrane fiber were studied. From this same apparatus,
values of the membrane permeability for hydroquinone, caffeine, theophylline, and
theobromine were found for cuprophan, cellulose acetate and polyacrylonitrile
membranes. A mathematical model was developed to determine the membrane
permeability, and it fit the data well.
The effects of inhibition of phenacetin and antipyrine metabolism in the liver
and acetylcholine metabolism in the brain on the amount of each substance lost from
the probe was studied. It was found through the development of a mechanistic model
that micro vasculature exchange rates dominate metabolism rates in the liver. Inhibition
of metabolism in the liver did not change the amount of material lost from the
microdialysis probe during a local infusion. Acetylcholine is removed from the brain
through only metabolic processes, thus inhibition affects the amount of material that
is lost from the microdialysis probe after a local infusion of acetylcholine in the brain.
A human study evaluated the usefulness of microdialysis for determining low
levels of caffeine taken ad lib. This final study shows that microdialysis sampling
although originally developed for brain studies in the rat, is finding more use in
human studies.
Description
This dissertation was digitized by the staff of the KU Libraries' Office of Scholarly Communication and Copyright.
Date
1995-10-11
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The University of Kansas