Abstract
The hydraulic resistances of the intima and media determine water flux and the advection of macromolecules into and across the arterial wall. Despite several experimental and computational studies, these transport processes and their dependence on transmural pressure remain incompletely understood. Here, we use a combination of experimental and computational methods to ascertain how the hydraulic permeability of the rat abdominal aorta depends on these two layers and how it is affected by structural rearrangement of the media under pressure. Ex vivo experiments determined the conductance of the whole wall, the thickness of the media and the geometry of medial smooth muscle cells (SMCs) and extracellular matrix (ECM). Numerical methods were used to compute water flux through the media. Intimal values were obtained by subtraction. A mechanism was identified that modulates pressure-induced changes in medial transport properties: compaction of the ECM leading to spatial reorganization of SMCs. This is summarized in an empirical constitutive law for permeability and volumetric strain. It led to the physiologically interesting observation that, as a consequence of the changes in medial microstructure, the relative contributions of the intima and media to the hydraulic resistance of the wall depend on the applied pressure; medial resistance dominated at pressures above approximately 93 mmHg in this vessel.
Highlights
The transport of molecules through the tissues comprising the arterial wall plays an important role in many processes ranging from lipid accumulation in atherosclerosis to contrast agent and drug transport in the diagnosis and treatment of disease
In our ex vivo experiments, the hydraulic conductance of the whole wall more than doubled as the transmural pressure difference increased from 40 to 80 mmHg but remained constant in the 80 –120 mmHg physiological range. (Note that Lp is defined as the flow per mmHg pressure gradient and that it accounts for changes in surface area but not wall thickness; if it remained constant as pressure increased resistance (×1011 kg s–1 m–2)
The extent of the distension will depend on the material properties of the wall; the thoracic aorta used in the four studies listed above is likely to be more elastic than the abdominal segment used here
Summary
The transport of molecules through the tissues comprising the arterial wall plays an important role in many processes ranging from lipid accumulation in atherosclerosis to contrast agent and drug transport in the diagnosis and treatment of disease. For many of these molecules, the Peclet number (Pe) is substantially greater than 1 [1,2] so their transport is dominated by advection, i.e. they are transported by the bulk flow of water. Studies of the anti-proliferative drug, paclitaxel, have shown the additional complexity that Pe is inhomogeneous through the arterial wall [3] Understanding such transport requires investigation of the local water transport.
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