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By Sandy F.C. Stewart, Center for Devices & Radiological Health, Food & Drug Administration, Rockville MD;
and Donald J. Lyman, Department of Materials Science & Engineering and Department of Bioengineering, University of Utah, Salt Lake City, UT
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Replacing diseased arteries with synthetic grafts, especially in large
vessels (to repair an aortic aneurysm, for example), has shown fairly
good success for almost fifty years. In small vessels (3.0 mm radius or
less) however, arterial grafts still have a much lower success rate, with failure
often due to tissue overgrowth (intimal hyperplasia) and clotting
(thrombosis), which block the vessel. Such failures are often seen primarily
at the downstream end of the graft. This asymmetry suggests that a flow
mechanism of some sort is responsible. Most commercially available synthetic
grafts are less compliant than natural arteries, so that the pulsating
blood must flow from the stiff graft region into the compliant artery. The
mismatch in compliance causes a pulsatile tubular expansion effect at the
downstream junction that can cause flow disturbances. A mismatch in
graft/artery radius (synthetic grafts only come in fixed radii) may also cause
a disruption in flow. It has been hypothesized that these flow disturbances
somehow trigger the intimal hyperplasia seen clinically, with thrombosis
following due to low or stagnating flow. Previous experimental and numerical
studies have shown that lower than normal wall shear stresses (WSSs),
trapping of particles (such as cells and other blood elements), and high
particle residence times are observed at junctions between a stiff graft and
compliant artery. Low WSS and the trapping of cells are known to be deleterious
to vessel walls and blood elements. Intimal hyperplasia may also be
triggered by the transport of chemicals in the blood, such as proteins, but
much less is known about this relationship.
Schematic of graft/artery model; the radial dimension (r) is scaled by a factor of ten;
the overall model is 0.24 cm radius x 9.5 cm long (reprinted with permission)
A numerical study was undertaken to examine the effects of compliance
and radius mismatch on the distribution of a representative protein
released into the blood at the graft/fluid interface. The protein chosen was
platelet-derived growth factor (PDGF), which has been shown to be
released from smooth muscle cells growing on the inner walls of vascular
grafts, and has been linked to intimal hyperplasia. FIDAP was used to simulate
pulsatile blood flow in an axisymmetric model of a synthetic graft
implanted into a natural artery. Fluid-structure coupling was employed to
give physiologic displacements of the vessel walls. PDGF was transported (by diffusion and convection) from a thin layer lining the inner wall of the
graft, using a diffusion constant calculated from its molecular weight. The
results are representative of similarly-sized molecules being transported by
the blood.
Protein concentration along the vessel inner wall at the end of the third cardiac
cycle (time = 2.5 s), at the downstream junction between the graft and artery
(reprinted with permission)
Minimum wall shear stress during the third cardiac cycle (time = 1.90 s), at the
downstream junction between the graft and artery (reprinted with permission)
Results showed that protein released from the graft is convected
smoothly downstream in a uniform compliant tube. A compliance mismatch
disturbs the protein transport, causing positive and negative gradients
in the concentration profile at the downstream junction. This was seen
whether or not the graft and artery radii were matched, but the disruption
was unexpectedly worse when the radii were matched. Disruptions in
WSSs were only observed when the radii were mismatched. Thus the
downstream intimal hyperplasia seen in noncompliant grafts may be
caused partly by decreased WSS, and partly by disruption of the concentration
gradients of dissolved chemicals, which can affect the movement of
cells (chemotaxis) in the blood.
Reference:
S.F.C. Stewart and D.J. Lyman, Effects of an Artery/Vascular Graft Compliance
Mismatch on Protein Transport: A Numerical Study, Ann. Biomed. Engr. 32,
p. 991-1006, 2004.
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