Biomedical subjects

S Weinbaum

Publications and source records attributed to S Weinbaum.

At least 19 recordsLinked to original sources

PubMed1997

A new fundamental bioheat equation for muscle tissue: Part I--Blood perfusion term.

A new model for muscle tissue heat transfer has been developed using Myrhage and Eriksson's [23] description of a muscle tissue cylinder surrounding secondary (s) vessels as the basic heat transfer unit. This model provides a rational theory for the venous return temperature for the perfusion source term in a modified Pennes bioheat equation, and greatly simplifies the anatomical description of the microvascular architecture required in the Weinbaum-Jiji bioheat equation. An easy-to-use closed-from analytic expression has been derived for the difference between the inlet artery and venous return temperatures using a model for the countercurrent heat exchange in the individual muscle tissue cylinders. The perfusion source term calculated from this model is found to be similar in form to the Pennes's source term except that there is a correction factor or efficiency coefficient multiplying the Pennes term, which rigorously accounts for the thermal equilibration of the returning vein. This coefficient is a function of the vascular cross-sectional geometry of the muscle tissue cylinder, but independent of the Peclet number in contrast to the recent results in Brinck and Werner [8]. The value of this coefficient varies between 0.6 and 0.7 for most muscle tissues. In part II of this study a theory will be presented for determining the local arterial supply temperature at the inlet to the muscle tissue cylinder.

Animals↗

PubMed1997

A model for the initiation and growth of extracellular lipid liposomes in arterial intima.

There is considerable evidence that lipoprotein cholesterol, after crossing the arterial endothelium and entering the intima from the vascular lumen, lodges in extracellular lipid packets (labeled "liposomes") bound to the extracellular matrix. These liposomes appear to form by occasional attachment of a low-density lipoprotein (LDL) to the intimal matrix and to grow in place mainly by appending available free LDL. The liposome size distributions observed in chronically hypercholesteremic (WHHL) and in short-term cholesterol-fed rabbits are quite different. We propose a hierarchy of simple nucleation-polymerization models to describe liposome formation and growth. Even the simplest of these (with only one adjustable parameter) agrees extremely well with the WHHL data. In contrast, the cholesterol-fed rabbit data seem to result from the short-term nonuniform intimal history of LDL supply, which is a consequence of the focal nature of the transendothelial LDL flow through isolated transient leakyjunctions. The same models used for the WHHL data, together with this intimal nonuniformity, superimposed on a slow uniform transendothelial seepage also account very well for this cholesterol-fed rabbit data.

Animals↗

PubMed1997

A fiber matrix model for the filtration through fenestral pores in a compressible arterial intima.

We advance a new hypothesis to explain the changes in hydraulic conductivity of an intact artery wall with transmural pressure previously observed by Tedgui and Lever [Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H784-H791, 1984] and Baldwin and Wilson [Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H26-H32, 1993]. This hypothesis suggests that compaction due to pressure loading of the proteoglycan matrix in the arterial intima near fenestral pores of the internal elastic lamina (IEL) leads to a narrowing of the pore entrance area and a large decrease in local intrinsic Darcy permeability of the matrix. To quantitatively assess the feasibility of this mechanism, a local two-dimensional model is proposed to study filtration flow in the vicinity of fenestral pores in a compressible intima. Using a heterogenous fiber matrix theory, we first predict the change in Darcy permeability with intimal thickness (Li). The model then calculates local velocity profiles and pressure distributions in the intima and media. The results show a marked nonlinear steepening of intimal pressure profiles near fenestral pores when the intima thins at higher luminal pressures. The predicted relative change in resistances of the IEL (with intima, R(I)) and of the media (Rm) shows a steep increase in R(I)/Rm when Li is <20% of its unstressed value. Numerical results also suggest that intimal compression has a limiting behavior in which the much stiffer collagen fibrils inhibit further compaction at high pressures after the proteoglycan matrix is maximally compressed. Predictions are also presented to show how different transmural pressures alter growth of an intimal horseradish peroxidase spot that derives from a localized (a single cell's boundary) endothelial leakage. Such a prediction is amenable to experimental verification.

Animals↗

PubMed1995

A case for bone canaliculi as the anatomical site of strain generated potentials.

We address the question of determining the anatomical site that is the source of the experimentally observed strain generated potentials (SGPs) in bone tissue. There are two candidates for the anatomical site that is the SGP source, the collagen-hydroxyapatite porosity and the larger size lacunar-canalicular porosity. In the past it has been argued, on the basis of experimental data and a reasonable model, that the site of the SGPs in bone is the collagen-hydroxyapatite porosity. The theoretically predicted pore radius necessary for the SGPs to reside in this porosity is 16 nm, which is somewhat larger than the pore radii estimated from gas adsorption data where the preponderance of the pores were estimated to be in the range 5-12.5 nm. However, this pore size is significantly larger than the 2 nm size of the small tracer, microperoxidase, which appears to be excluded from the mineralized matrix. In this work a similar model, but one in which the effects of fluid dynamic drag of the cell surface matrix in the bone canaliculi are included, is used to show that it is possible for the generation of SGPs to be associated with the larger size lacunar-canalicular porosity when the hydraulic drag and electrokinetic contribution of the bone fluid passage through the cell coat (glycocalyx) is considered. The consistency of the SGP data with this model is demonstrated. A general boundary condition is introduced to allow for current leakage at the bone surface. The results suggest that the current leakage is small for the in vitro studies in which the strain generated potentials have been measured.

Biomechanical Phenomena↗

PubMed1995

A non-uniform three-dimensional perfusion model of rat tail heat transfer.

Previous models of rat tail heat transfer have assumed that the tail is uniformly perfused along its length and have introduced questionable assumptions about the heat transfer role of the major axial arteries and the venous blood shunting between the superficial and deep veins. The recent experiments of Lemons and Wu have shown that (i) perfusion of the tail tip is more than tenfold higher than that in the tail base and (ii) the perfusion of the middle region of the tail increases eightfold during heat stress compared to threefold to fourfold in the base and tip. Our anatomical studies have shown that the lateral arteries are a series of radially arcading connections from the ventral artery and probably do not serve as major axial conduit vessels. These observations indicate that current views and models for the blood flow distribution and heat transfer in the major axial arteries and veins and in the rat tail cutaneous circulation need substantial revision. Based on these new experimental findings a new three-dimensional model is developed to determine the heat transfer function of the rat tail at different local and central temperatures. The predictions of the model show good agreement with the axial surface temperature distribution in the rat tail reported by Lemons and Wu. These results, when combined with our anatomical studies, indicate that there is very little shunting of blood between the superficial lateral veins and the deep ventral vein as proposed by Raman et al. Although this model is based on the rat tail anatomy, it can be modified to treat the human limb and digit.

Animals↗

PubMed1995

A model for heat transfer from embedded blood vessels in two-dimensional tissue preparations.

Two-dimensional microvascular tissue preparations have been extensively used to study blood flow in the microcirculation, and, most recently, the mechanism of thermal equilibration between thermally significant countercurrent artery-vein pairs. In this paper, an approximate three-dimensional solution for the heat transfer from a periodic array of blood vessels in a tissue preparation of uniform thickness with surface convection is constructed using a newly derived fundamental solution for a Green's function for this flow geometry. This approximate solution is exact when the ratio K' of the blood to tissue conductivity is unity and a highly accurate approximation when K' not equal to 1. This basic solution is applied to develop a model for the heat transfer from a countercurrent artery-vein pair in an exteriorized rat cremaster muscle preparation. The numerical results provide important new insight into the design of microvascular experiments in which the axial variation of the thermal equilibration in microvessels can be measured for the first time. The solutions also provide new insight into the design of fluted fins and microchips that are convectively cooled by internal pores.

Animals↗

PubMed1995

A diffusion wake model for tracer ultrastructure-permeability studies in microvessels.

We developed a time-dependent diffusion model for analyzing the concentration profiles of low-molecular-weight tracers in the interendothelial clefts of the capillary wall that takes into account the three-dimensional time-dependent filling of the surrounding tissue space. The model provides a connecting link between two methods to investigate transvascular exchange: electron-microscopic experiments to study the time-dependent wake formed by low-molecular-weight tracers (such as lanthanum nitrate) on the tissue side of the junction strand discontinuities in the interendothelial cleft of frog mesentery capillaries (R. H. Adamson and C. C. Michel. J. Physiol. Lond. 466: 303-327, 1993) and confocal-microscopic experiments to measure the spread of low-molecular-weight fluorescent tracers in the tissue space surrounding these microvessels (R. H. Adamson, J. F. Lenz, and F. E. Curry, Microcirculation 1: 251-265, 1994). We show that the interpretation of the presence of tracer as an all-or-none indication of a pathway across the junctional strand is likely to be incorrect for small solutes. Large-pore pathways, in which the local tracer flux densities are high, reach a threshold concentration for detection and are likely to be detected after relatively short perfusion times, whereas distributed small-pore pathways may not be detected until the tissue concentrations surrounding the entire vessel approach threshold concentrations. The analysis using this approach supports the hypothesis advanced by Fu et al. (J. Biomech. Eng. 116: 502-513, 1994) that the principal pathways for water and solutes of < 1.0 nm diameter across the interendothelial cleft may be different and suggests new experiments to test this hypothesis.

Blood Vessels↗

PubMed1995

Modelling the structural pathways for transcapillary exchange.

The ultrastructural pathways and mechanisms whereby endothelial cells and the clefts between the cells modulate capillary permeability to water and solutes have been a central unresolved question in microvessel transport since the early 1950s. Freeze-fracture studies and ultrathin serial sections have demonstrated that endothelial cells are joined by an array of junctional strands which are interrupted at intervals, allowing for the passage of water and solutes, whereas cytochemical studies have indicated that the endothelial surface and portions of the wide part of the cleft contain matrix components. Neither constricted slit models based on the classic pore theory nor fiber matrix models are able to explain the large body of existing permeability measurements. In this review, we shall describe new three-dimensional modelling approaches which have resulted in a major revision of current ideas about the pathways for water and solutes through the junction strand and the structures that determine the molecular filter. For frog mesentery capillaries, these models predict (i) that the primary pathway for small ions is a previously unrecognized family of 2nm small pores that are distributed along the length of the junction strand; (ii) that the primary pathway for water and intermediate-sized solutes (1-3.5 nm radius) is an infrequent 150 nm long orifice-like pore whose height is the same as that of the wide part of the cleft; (iii) that the sieving structure for these solutes is a fiber layer, typically 100 nm thick, which extends from the surface into the entrance region of the cleft and (i.v.) that the interpretation of low molecular weight tracer studies to define the permeability pathways depends on the time-dependent filling of the extravascular space.

Animals↗

PubMed1994

A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses.

A new experimentally testable hypothesis is advanced for the mechanosensory transduction mechanism by which communicating osteocytes sense the very small in vivo strains in the calcified matrix components of bone. We propose that the osteocytes, although not responsive to substantial fluid pressures, can be stimulated by relatively small fluid shear stresses acting on the membranes of their osteocytic processes. Biot's porous media theory is used to relate the combined axial and bending loads applied to a whole bone to the flow past the osteocytic processes in their canaliculi. In this theory, the bone pores of interest are the proteoglycan filled fluid annuli that surround the osteocytic processes in the canaliculi. We show that previously predicted fluid pore pressure relaxation times were a hundred-fold too short for the lacunar-canalicular porosity because they neglected the fluid drag associated with proteoglycan matrix on the surface membrane of the osteocyte and its cell processes. The recent theory developed in Tsay and Weinbaum [J. Fluid Mech. 226, 125-148 (1991)] for flow through cross-linked fiber filled channels is used to model the flow through this proteoglycan matrix. The predicted pore relaxation time, 1-2 s, closely corresponds to the times measured by Salzstein and Pollack [J. Biomechanics 20, 271-280 (1987)]. Furthermore, using this model, the magnitude of the predicted fluid induced shear stresses, 8-30 dyn cm-2, is shown to be similar to the fluid shear stresses measured in osteoblasts and other cells in which an intracellular Ca2+ shear stress response had been observed. This model is also used, in conjunction with anatomical data and the pore fluid pressure relaxation time data, to show that the spacing between the fibers is approximately 7 nm. The result is consistent with the notion that the canalicular pore space is filled with glycosaminoglycans that are ordered by albumin according to the model of Michel [J. Physiol. 404, 1-29 (1988)]. The new hypothesis is also shown to be consistent with the experiments of McLeod et al. [J. Biomechanics (submitted)] which suggest that high-frequency low-amplitude postural strains can maintain and even increase bone mass.

Animals↗

PubMed1994

A fiber matrix model for the growth of macromolecular leakage spots in the arterial intima.

A new model is presented for the growth of cellular level macromolecular leakage spots in the arterial intima. The theoretical approach differs from the recent study by Yuan et al. [19] in that it directly models and calculates the intimal transport parameters based on Frank and Fogelman's [22] ultrastructural observations of the extracellular subendothelial proteoglycan matrix that their rapid freeze etching technique preserves (see Addendum). Using a heterogeneous fiber matrix theory, which includes proteoglycan and collagen components, the model predicts that the Darcy permeability Kp and macromolecular diffusivity D of the subendothelial intima is two orders of magnitude larger than the corresponding values measured in the media, and supports the observations in Lark et al. [24] that the proteoglycan structure of the intima differs greatly from that of the media. Numerical results show that convection parallel to the endothelium is a very significant transport mechanism for macromolecules in the intima in a large region of roughly 200 microns diameter surrounding the leaky cleft. The predictions of the new model for the early-time spread of the advancing convective-diffusive front from the leakage spots in the intima are in close agreement with our experimental measurements for the growth of HRP spots in [20]. The regions of high concentration surrounding the leaky cell, however, are much more limited and cover an area that is typically equivalent to 20 cells. This prediction is consistent with the recent measurements of Truskey et al. for LDL spot size in rabbit aorta [21] and the hypothesis advanced in [19] that there is a colocalization of subendothelial liposome growth and cellular level leakage. Finally, comparison of predicted and experimentally-measured average LDL concentration in leakage spots strongly suggests that there is significant local molecular sieving at the interface between the fenestral openings in the internal elastic lamina and the media.

Animals↗

PubMed1994

A junction-orifice-fiber entrance layer model for capillary permeability: application to frog mesenteric capillaries.

The recent serial section electron microscopic studies by Adamson and Michel (1993) on microves gels of frog mesentery have revealed that the large pores in the junction strand of the interendothelial cleft are widely separated 150 nm wide orifice-like breaks whose gap height 20 nm is the same as the wide part of the cleft. In this paper a modified version of the model in Weinbaum et al. (1992) is first developed in which this orifice structure is explored in combination with a random or ordered fiber matrix layer that is at the luminal surface and/or occupies a fraction of the wide part of the cleft. This basic orifice model predicts that for the measured Lp to be achieved the fiber layer must be confined to a relatively narrow region at the entrance to the cleft where it serves as the primary molecular filter. The model provides a much better fit of the permeability P for intermediate size solutes between 1 and 2 nm radius than the previous model in Weinbaum et al., where the junction strand breaks were treated as finite depth circular or rectangular pores, but like the previous model significantly underestimates P for small ions. However, it is shown that if a small frequent pore of 1.5 nm radius with characteristic spacing comparable to the diameter of the junction proteins or a continuous narrow slit of approximately 1.5 to 2.3 nm gap height is also present in the continuous part of the junction strand, small ion permeability can also be satisfied. The 1.5 nm radius pore does not significantly change Lp, whereas the continuous narrow slit provides a contribution to Lp that is comparable to, or in the case of the 2.3 nm slit greater than, the widely spaced 150 nm orifices. Thus, for the narrow slit the contribution to Lp from the orifices can be as low as 1.0 x 10(-7) cm/s/cm H2O and it is also possible to satisfy the 2.5 fold increase in permeability that occurs when the matrix is enzymatically removed from the luminal side of the cleft, Adamson (1990). The likelihood of each of these cleft structures is discussed.

Animals↗

PubMed1993

Lipid transport aspects of atherogenesis.

In this review we shall examine the current understanding of events that lead to the incipient formation of the early foam cell lesion in atherogenesis and its localization. Particular emphasis will be placed on the intimal transport mechanisms that lead to the growth of extracellular lipid liposomes in the intima, since there is now substantial evidence that this growth is the triggering event in the complex sequence of processes that leads to the recruitment of blood borne monocytes into the subendothelial intima and their subsequent conversion to macrophages. The role of the endothelium, intimal proteoglycans and internal elastic lamina (IEL) in modulating the transport of low density lipoproteins (LDL) in the subendothelial space will be analyzed and a new hypothesis for the co-localization of liposome formation, cellular level endothelial leakage and monocyte entry described. The possible modifications of LDL in the liposomes that facilitate the conversion of monocytes into foam cells is summarized. We also discuss the fluid dynamic aspects of intimal transport and the relationship of fluid shear stress to the localization of cellular level endothelial leakage of LDL. The effect of fluid shear on other endothelial cell functions has been recently reviewed in [1].

Animals↗

PubMed1992

A three-dimensional junction-pore-matrix model for capillary permeability.

A three-dimensional model is presented for the hydraulic conductivity and diffusive permeability of capillary endothelial clefts with a junctional strand with discrete pores and a fiber matrix in its wide parts. The model attempts to provide new insight into long-standing issues concerning the relative importance of open junction discontinuities, restricted slit regions, and matrix components in determining the permeability and selectivity of the capillary wall. The predictions drawn from the model are used to formulate new experiments to test two hypotheses concerning the molecular organization of the junction strand and the location of matrix structures in the wide part of the cleft. Using the three-dimensional theoretical approach recently developed by Tsay, Weinbaum, and Pfeffer (Chem. Eng. Comm. 82, 67-102, 1989), the model first explores the behavior of three different molecular models for the junctional strand discontinuities: (i) a more frequent circular pore of 5.5-nm radius formed by isolated missing junction proteins; (ii) a restricted rectangular slit of four to eight missing proteins and 8-nm gap height; and (iii) larger more infrequent breaks of four to eight missing proteins with a gap height of 22 nm, equal to the width of the wide part of the cleft. For the circular and 8-nm gap height pores the primary molecular sieve can be located at the level of the junction strand, whereas for the 22-nm gap height pores, matrix components must be present in at least some portion of the cleft to provide the molecular filter. The water flow through the cross-bridging fibers in the wide part of the cleft is described either by a new exact three-dimensional theory (Tsay and Weinbaum, J. Fluid Mech. 226, 125-148, 1991) for an ordered periodic array or by a new approximate theory for a random array of perpendicular fibers. Both this theory and the new approximate theory for diffusion presented herein take into account for the first time the interaction between the fibers and plasmalemma boundaries. The principal predictions of the model are that (i) infrequent larger breaks are most likely required to account for small solute permeability; (ii) these larger breaks must be accompanied by a sieving matrix, but this matrix probably occupies only a small portion of the depth of the cleft and/or its entrance at the luminal surface; (iii) neither junctional pore, restricted slit, or fiber matrix models can by themselves satisfy permeability and selectivity data; and (iv) one-dimensional models are a poor description of a cleft with infrequent larger breaks since the solute will be confined to small wakelike regions on the downstream side of the junction strand discontinuities and thus not fill the wide part of the cleft.

Capillary Permeability↗

PubMed1992

A three-dimensional variable geometry countercurrent model for whole limb heat transfer.

A new formulation of the combined macro and microvascular model for heat transfer in a human arm developed in Song et al. [1] is proposed using a recently developed approximate theory for the heat exchange between countercurrent vessels embedded in a tissue cylinder with surface convection [2]. The latter theory is generalized herein to treat an arm with an arbitrary variation in cross-sectional area and continuous bleed off from the axial vessels to the muscle and cutaneous tissue. The local microvascular temperature field is described by a "hybrid" model which applies the Weinbaum-Jiji [3] and Pennes [4] equations in the peripheral and deeper tissue layers, respectively. To obtain reliable end conditions at the wrist and other model input parameters, a plethysmograph-calorimeter has been used to measure the blood flow distribution between the arm and hand circulations, and hand heat loss. The predictions of the model show good agreement with measurements for the axial surface temperature distribution in the arm and confirm the minimum in the axial temperature variation first observed by Pennes [4] for an arm in a warm environment.

Arm↗

PubMed1992

The bleed off perfusion term in the Weinbaum-Jiji bioheat equation.

The microvascular organization and thermal equilibration of the primary and secondary arteries and veins that comprise the bleed off circulation to the muscle fibers from the parent countercurrent supply artery and veins are analyzed. The blood perfusion heat source term in the tissue energy equation is shown to be related to this vascular organization and to undergo a fundamental change in behavior as one proceeds from the more peripheral tissue, where the perfusion term is proportional to the Ta--Tv difference in the parent supply vessels, to the deeper tissue layers where the bleed off vessels themselves form a branching countercurrent system for each muscle tissue cylinder and the venous return temperature can vary between the local tissue temperature and Ta. The consequences of this change in behavior are examined for the Weinbaum-Jiji bioheat equation and a modified expression for the effective conductivity of perfused tissue is derived for countercurrent bleed off exchange.

Body Temperature Regulation↗

PubMed1991

A three-dimensional analysis of plasma skimming at microvascular bifurcations.

This paper analyzes an important underlying mechanism for the discharge hematocrit reduction observed in microvessels, which refers to the plasma skimming from the cell-free layer near the parent tube wall in the presence of a side branch. The three-dimensional theory recently developed by the authors (Yan et al., 1991, J. Fluid Mech., in press) for treating the simple shear flow past a side branch tube in a plane wall with suction is first summarized and then extended to treat T bifurcations from parent vessels with an upstream Poiseuille flow. For unequal vessel bifurcations, a fundamental new dimensionless group, Q = 1/8(qb/qp)(Rp/Rb)3, is derived whose value determines the shape of the upstream capture tube of the plasma phase, when the partitioning qb/qp of the flow into the side branch and the ratio Rp/Rb of the radii of the parent and side branch vessels are varied. Closed form expressions are then presented for the three-dimensional fluid capture tube shape upstream of the bifurcation which are valid when Q greater than 1 or Q less than 0.2. Based on this theory and its modification for an upstream Poiseuille velocity profile, the separating surface shape, the critical minimum fractional flux for incipient cell capture, and the discharge hematocrit defect and its dependence on the flow rate are predicted. It is shown, furthermore, that for flows typical of the microcirculation, a single dimensionless number, P = 3 pi Q(Rb/gamma 2), with gamma being the cell-free layer thickness, can be defined whose value determines the discharge hematocrit defect that arises from plasma skimming. The minimum critical flow rate for any red cells to enter the side branch is then given by the criterion P = 1. Although this theory does not account for the cell screening effect arising from the hydrodynamic interaction between the cells and the tube walls, it leads to predictions which exhibit the same trends as the experimental observations and is able to explain the results of several seemingly contradictory microvascular experiments that have puzzled investigators in recent years.

Hematocrit↗

PubMed1991

A mathematical model for the receptor mediated cellular regulation of the low density lipoprotein metabolism.

A prototype mathematical model for Brown and Goldstein's pioneering studies on the LDL receptor mediated pathway for the regulation of the cellular content of cholesterol has been developed in this paper. In order to analyze the essential features of this complex system quantitatively and still reflect the framework of the total system, six important processes are considered in the model. They are: (1A, B) the hydrolysis and synthesis of the LDL receptor; (2) the binding of LDL to its receptors; (3) the hydrolysis of LDL; (4) the storage of cholesteryl esters; (5) the regulation of de novo synthesis of cholesterol; and (6) the efflux of free cholesterol to the external medium. All these processes form a system to let the cells take up enough cholesterol from the external medium for their utilization and yet avoid the excessive accumulation of the lipid within the cells. The validity of the model is tested by showing that it can predict many of experimental curves obtained for human fibroblasts in tissue culture studies. The main purpose of the model is to determine how the free cholesterol level in the cell is related to the external LDL concentration and the regulatory capacity of the cells to adapt to a changing LDL environment. In addition, the model reveals an important behavior of SMC, i.e., for a slowly increasing LDL concentration in the extracellular medium, the rate of intracellular degradation of LDL will first increase and then become saturated. It is proposed based on these results that the saturation of LDL degradation by SMCs and the subsequent increase in subendothelial LDL levels in regions of high macromolecular permeability might play a vital role in the formation of the early foam cell lesion.

Cells, Cultured↗

PubMed1991

A new view of convective-diffusive transport processes in the arterial intima.

In this paper a new theoretical framework is presented for analyzing the filtration and macromolecular convective-diffusive transport processes in the intimal region of an artery wall with widely dispersed macromolecular cellular leakage sites, as proposed in the leaky junction-cell turnover hypothesis of Weinbaum et al. In contrast to existing convection-diffusive models, which assume that the transport is either 1-D, or convection is primarily in a direction normal to the endothelial surface, the present model considers for the first time the nonuniform subendothelial pressure field that arises from the different hydraulic resistances of normal and leaky endothelial clefts and the special role of the internal elastic lamina (IEL) in modulating the horizontal transport of macromolecules after they have passed through the leaky clefts of cells that are either in mitosis or demonstrate IgG labeling. The new theory is able to quantitatively explain the growing body of recent experiments in which an unexpectedly rapid early-time growth of the leakage spot has been observed and the longer time asymptotic behavior in which the leakage spot appears to approach an equilibrium diameter. The new theory also predicts the observed doubling in macromolecular permeability between EBA labeled blue and white areas when the frequency of leakage sites is doubled. This frequency for doubling of permeability, however, is an order of magnitude smaller than predicted by the author's previous model, Tzeghai et al., in which only convection normal to the endothelial surface was considered and the pressure was uniform in the intima. The longer time model predictions are used to explain the time scale for the formation of liposomes in subendothelial tissue matrix in animal feeding experiments where it has been observed that the extracellular lipid concentration rises sharply prior to the entry of monocytes into the intima.

Arteries↗