Biomedical Engineering Reference
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ultrastructure using serial section electron microscopy. Later, Ward et al. [ 83 ]
examined the 3D features of the junction strands of rat cardiac capillaries by using
a goniometric tilting technique. Based on the study of Bundgaard [ 13 ]andWard
et al. [ 83 ], Tsay and Weinbaum [ 79 ] and Weinbaum et al. [ 84 ] proposed a basic 3D
model for the interendothelial cleft. Their 3D treatments showed that 1D models
are a poor description of a cleft with infrequent large breaks since the solute will be
confined to small wake-like regions on the downstream side of the junction strand
discontinuities and thus not fill the wide part of the cleft. The prediction in
Weinbaum et al. [ 85 ] as to the likely geometry of the large pores in the junction
strand was confirmed by the serial section electron microscopic study on frog
mesenteric capillaries in Adamson and Michel [ 2 ] . According to these new
experimental results, a modified combined junction-orifice-fiber entrance layer
model(describedinFig. 4.3 ),whichincludedalargeorifice-like junctional break
with the width 2 d and height 2 B , spaced 2 D apart, a finite region of fiber matrix
components (with the thickness L f ) at the entrance of the cleft and very small
pores or slits (with the height 2 b s ) in the continuous part of the junction strand,
was developed by Fu et al. [ 28 ]. Using this combined junction-orifice-fiber
entrance layer model it was predicted that in order to provide an excellent fit for
the hydraulic conductivity and the diffusive permeability data for solutes of size
ranging from potassium to albumin for frog mesenteric capillaries, there should
be a significant fiber layer at the luminal side of the endothelium, together
with large infrequent breaks of ~150 nm and a continuous small slit of several
nm in the junction strand in the interendothelial cleft. Due to the similarity in
morphological wall structure of microvessels in different tissues [ 57 ], this 3D
model can be easily adapted to explain the permeability data in other types of
microvessels [ 46 , 48 , 52 , 89 ]. Fu et al. [ 27 ] in another work described a new
approach to explore junction strand structure. The time dependent diffusion
wake model in Fu et al. [ 27 ] provided a new interpretation of labeled tracer
studies to define the permeability pathways for low molecular weight tracers
which depend on the time dependent filling of the extravascular space.
In Fu et al. [ 26 ] a time dependent convective-diffusion wake model for high
molecular weight tracers was proposed to design experiments that could test for
the location of the molecular filter. Combined with the experimental results,
this model confirmed the role of the ESG as the primary molecular filter to
large molecules and particles. Hu and Weinbaum [ 42 ] also showed that coupling
of water flow to albumin flux on the tissue side of the ESG could give rise to a
nonuniform distribution of albumin concentration and a corresponding nonuni-
form distribution of effective osmotic pressure. A similar model for oncotic
pressures opposing filtration across rat microvessels [ 1 ] further confirms the
hypothesis that colloid osmotic forces opposing filtration across non-fenestrated
continuous capillaries are developed across the ESG and that the oncotic
pressure of interstitial fluid does not directly determine fluid balance across the
microvascular endothelium.
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