Award Date

1-1-2004

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Mechanical Engineering

First Committee Member

Bingmei Fu

Number of Pages

145

Abstract

Vascular endothelium is the principal barrier to, and regulator of, material exchange between circulating blood and the body tissues. Both the endothelial surface glycocalyx and the glycosaminoglycans in the tissue carry negative charge. However, none of the previous studies considered these charge effects on water and solute transport across the endothelium and in the tissue. It is important to understand how charge affects the water and solute transport across the endothelial barriers and in the interstitium because it may provide strategies for controlling transport of charged or uncharged macromolecules in drug delivery; In the first part of this dissertation, to investigate the mechanisms of how surface properties of the endothelial cells control the changes in microvessel permeability, the charge-diffusion model developed by Fu et al. (2003b) for the interendothelial cleft with a negatively charged surface glycocalyx layer is extended to include the filtration due to hydrostatic and oncotic pressures across the microvessel wall, as well as the electrical potential across the surface fiber layer. This charge-diffusion-filtration model provides a good agreement with experimental data for permeability of negatively charged alpha-lactalbumin summarized in Curry (1994) under various conditions. Furthermore, this model is applied to describe the transport of negatively charged macromolecules, bovine serum albumin and low density lipoprotein (LDL), across the frog mesenteric microvessels under normal microvessel permeability and when the permeability is increased by ionophore A23187; In the second part of this dissertation, to investigate the mechanisms of how negative charge of the interstitium affects the charged solute transport in the interstitium, the model in the first part of this dissertation is extended and a time-dependent electrodiffusion-filtration model for macromolecule transport in the interstitium is developed. The model predictions explain the experimental results in Fu et al. (2003c), which described the temporal and spatial distribution of alpha-lactalbumin transport in the frog mesenteric tissue. This model also illustrates that the apparent interstitial diffusion coefficient of negatively charged albumin in the mesenteric tissue is found comparable to that of neutral dextran with equivalent hydrodynamic radius. The discrepancy of their concentration distribution in the tissue space, which was obtained in Fox and Wayland (1979) and Nugent and Jain (1984) can be explained by the fixed negative charge in the tissue instead of different diffusion coefficients.

Keywords

Barriers; Charge; Diffusion; Endothelial; Endothelial Barriers; Filtration; Glycocalyx; Interstitial; Interstitial Space; Models; Space; Transport

Controlled Subject

Biomedical engineering; Mechanical engineering; Physiology

File Format

pdf

File Size

3205.12 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

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