Microvascular Permeability and Tumor Metastasis - Bioanalysis Advanced Materials Methods and Devices - page 53

in pressure and concentration, they usually involve minimal interference with the
microvessels themselves. These studies can provide valuable information
concerning microvascular exchange under basal conditions. At the other extreme
are measurements on single perfused vessels. The hydraulic conductivity L p and
reflection coefficient s have been measured using the Landis technique and the
solute diffusive permeability P using quantitative fluorescence microscope pho-
tometry. Both of these techniques are described in detail in [ 57 ]. The surface area of
the microvessel can be measured directly, as also can the difference in pressure and
concentration across the vessel walls. The disadvantages of the single vessel
preparation are (1) that they have direct interference with the vessels involved,
and (2) that they are usually restricted to a small number of convenient vessel types
(e.g., mesenteric vessels on a two dimensional translucent tissue). Direct interfer-
ence with a vessel, whether it is exposure to light or micromanipulation, might be
expected to increase permeability. However, this concern was allayed when it was
shown that L p and P for potassium ions in single muscle capillaries were similar to
values based on indirect measurements on the intact muscle microcirculation [ 57 ].
Although the rapid growth of endothelial cell biology is largely a result of
experiments on cultured endothelial cells in vitro (in dishes), there are limitations
to the use of monolayers of cultured endothelial cells for gaining direct information
about vascular permeability. In general, the in vitro permeability to albumin is two
to ten times larger than that from the in vivo (in live animals) measurement.
Although the monolayers of cultured endothelial cells do not completely reflect
the permeability characteristics of microvascular endothelium in vivo, they are the
most accessible and convenient models for studying the molecular mechanisms by
which the microvascular permeability is regulated. The techniques for measuring
endothelial monolayer permeability to water and solutes are described in [ 5 , 14 , 47 ].

4.3 Transport Models for the Interendothelial Cleft

4.3.1 1D Models

Prior to the late 1980s, there were two major 1D theories which attempted to
correlate cleft structure with the large amount of experimental data for L p , P , and
s —the pore-slit and the fiber matrix theory. In microvessels with a continuous
endothelium, the principal pathway for water and solutes lies between the endothe-
lial cells through the interendothelial cleft. 1D pore-slit models were developed
in terms of the ultrastructure of the cleft.
In the pore-slit theory, the permeability properties of the microvessel wall can
be described in terms of flow through water-filled cylindrical pores or rectangular
slits through the vessel wall. A Poiseuille type viscous flow was assumed in the
pore/slit to describe the resistance to water flow, with the characteristic Reynolds
number for the flow of the order of 10 8 . The resistance to solute diffusion can be