Research studies over the last three decades have established that hemodynamic interactions with the vascular surface as well as surgical injury are inciting mechanisms capable of eliciting distal anastomotic intimal hyperplasia (IH) and ultimate bypass graft failure. While abnormal wall shear stress (WSS) conditions have been widely shown to affect vascular biology and arterial wall self-regulation, the near-wall localization of critical blood particles by convection and diffusion may also play a significant role in IH development. It is hypothesized that locations of elevated platelet interactions with reactive or activated vascular surfaces, due to injury or endothelial dysfunction, are highly susceptible to IH initialization and progression. In an effort to assess the potential role of platelet-wall interactions, experimentally validated particle-hemodynamic simulations have been conducted for two commonly implemented end-to-side anastomotic configurations, with and without proximal outflow. Specifically, sites of significant particle interactions with the vascular surface have been identified by a novel near-wall residence time (NWRT) model for platelets, which includes shear stress-based factors for platelet activation as well as endothelial cell expression of thrombogenic and anti-thrombogenic compounds. Results indicate that the composite NWRT model for platelet-wall interactions effectively captures a reported shift in significant IH formation from the arterial floor of a relatively high-angle (30 deg) graft with no proximal outflow to the graft hood of a low-angle graft (10 deg) with 20% proximal outflow. In contrast, other WSS-based hemodynamic parameters did not identify the observed system-dependent shift in IH formation. However, large variations in WSS-vector magnitude and direction, as encapsulated by the WSS-gradient and WSS-angle-gradient parameters, were consistently observed along the IH-prone suture-line region. Of the multiple hemodynamic factors capable of eliciting a hyperplastic response at the cellular level, results of this study indicate the potential significance of platelet-wall interactions coinciding with regions of low WSS in the development of IH.

1.
Sottiurai
,
V. S.
,
Yao
,
J. S. T.
,
Flinn
,
W. R.
, and
Batson
,
R. C.
,
1983
, “
Intimal Hyperplasia and Neointima: An Ultrastructural Analysis of Thrombosed Grafts in Humans
,”
Surgery
,
93
(
6
), pp.
809
817
.
2.
Bassiouny
,
H. S.
,
White
,
S.
,
Glagov
,
S.
,
Choi
,
E.
,
Giddens
,
D. P.
, and
Zarins
,
C. K.
,
1992
, “
Anastomotic Intimal Hyperplasia: Mechanical Injury or Flow Induced
,”
J. Vasc. Surg.
,
15
, pp.
708
717
.
3.
Keynton
,
R. S.
,
Rittgers
,
S. E.
, and
Shu
,
M. C. S.
,
1991
, “
The Effect of Angle and Flow Rate Upon Hemodynamics in Distal Vascular Graft Anastomoses: An In Vitro Model Study
,”
ASME J. Biomech. Eng.
,
113
, pp.
458
463
.
4.
Kleinstreuer
,
C.
,
Hyun
,
S.
,
Buchanan
,
J. R.
,
Longest
,
P. W.
,
Archie
,
J. P.
, and
Truskey
,
G. A.
,
2001
, “
Hemodynamic Parameters and Early Intimal Thickening in Branching Blood Vessels
,”
Crit. Rev. Biomed. Eng.
,
29
(
1
), pp.
1
64
.
5.
Ojha
,
M.
,
Ethier
,
C. R.
,
Johnston
,
K. W.
, and
Cobbold
,
R. S. C.
,
1990
, “
Steady and Pulsatile Flow Fields in an End-to-Side Arterial Anastomosis Model
,”
J. Vasc. Surg.
,
12
, pp.
747
753
.
6.
Ojha
,
M.
,
Cobbold
,
R. S. C.
, and
Johnston
,
K. W.
,
1994
, “
Influence of Angle on Wall Shear Stress Distribution for an End-to-Side Anastomosis
,”
J. Vasc. Surg.
,
19
, pp.
1067
1073
.
7.
Sottiurai
,
V. S.
,
1999
, “
Distal Anastomotic Intimal Hyperplasia: Histocytomorphology, Pathophysiology, Etiology, and Prevention
,”
International Journal of Angiology
,
8
, pp.
1
10
.
8.
Leuprecht
,
A.
,
Perktold
,
K.
,
Prosi
,
M.
,
Berk
,
T.
,
Trubel
,
W.
, and
Schima
,
H.
,
2002
, “
Numerical Study of Hemodynamics and Wall Mechanics in Distal End-to-Side Anastomoses of Bypass Grafts
,”
J. Biomech.
,
35
, pp.
225
236
.
9.
Trubel
,
W.
,
Schima
,
H.
,
Moritz
,
A.
,
Raderer
,
F.
,
Windisch
,
A.
,
Ullrich
,
R.
,
Windberger
,
U.
,
Losert
,
U.
, and
Polterauer
,
P.
,
1995
, “
Compliance Mismatch and Formation of Distal Anastomotic Intimal Hyperplasia in Externally Stiffened and Lumen-Adapted Venous Grafts
,”
Eur. J. Vasc. Endovasc Surg.
,
10
, pp.
1
9
.
10.
White
,
S. S.
,
Zarins
,
C. K.
,
Giddens
,
D. P.
,
Bassiouny
,
H.
,
Loth
,
F.
,
Jones
,
S. A.
, and
Glagov
,
S.
,
1993
, “
Hemodynamic Patterns in Two Models of End-to-Side Vascular Graft Anastomoses: Effects of Pulsatility, Flow Division, Reynolds Number, and Hood Length
,”
ASME J. Biomech. Eng.
,
115
, pp.
104
111
.
11.
Sottiurai
,
V. S.
,
Yao
,
J. S. T.
,
Batson
,
R. C.
,
Sue
,
S. L.
,
Jones
,
R.
, and
Nakamura
,
Y. A.
,
1989
, “
Distal Anastomotic Intimal Hyperplasia: Histopathologic Character and Biogenesis
,”
Ann. Vasc. Surg.
,
3
(
1
), pp.
26
33
.
12.
Keynton
,
R. S.
,
Evancho
,
M. M.
,
Sims
,
R. L.
,
Rodway
,
N. V.
,
Gobin
,
A.
, and
Rittgers
,
S. E.
,
2001
, “
Intimal Hyperplasia and Wall Shear in Arterial Bypass Graft Distal Anatomoses: An In Vivo Model Study
,”
J. Biomech. Eng.
,
123
, pp.
464
473
.
13.
Li
,
X.
, and
Rittgers
,
S. E.
,
2001
, “
Hemodynamic Factors at the Distal End-to-Side Anastomosis of a Bypass Graft With Different POS:DOS Flow Ratios
,”
ASME J. Biomech. Eng.
,
123
, pp.
270
276
.
14.
Loth
,
F.
,
Jones
,
S.
,
Zarins
,
C. K.
,
Giddens
,
D. P.
,
Nassar
,
R. F.
,
Glagov
,
S.
, and
Bassiouny
,
H. S.
,
2002
, “
Relative Contribution of Wall Shear Stress and Injury in Experimental Intimal Thickening at PTFE End-to-Side Arterial Anastomoses
,”
J. Biomech. Eng.
,
124
, pp.
44
51
.
15.
Longest
,
P. W.
,
Kleinstreuer
,
C.
,
Truskey
,
G. A.
, and
Buchanan
,
J. R.
,
2003
, “
Relation Between Near-Wall Residence Times of Monocytes and Early Lesion Growth in the Rabbit Aorto-Celiac Junction
,”
Ann. Biomed. Eng.
,
31
, pp.
53
64
.
16.
Harrison
,
D. G.
,
Sayegh
,
H.
,
Ohara
,
Y.
,
Inoue
,
N.
, and
Venema
,
R. C.
,
1996
, “
Regulation of Expression of the Endothelial Cell Nitric Oxide Synthase
,”
Clin. Exp. Pharmacol. Physiol.
,
23
, pp.
251
255
.
17.
Mondy
,
J. S.
,
Lindner
,
V.
,
Miyashiro
,
J. K.
,
Berk
,
B. C.
,
Dean
,
R. H.
, and
Geary
,
R. L.
,
1997
, “
Platelet-Derived Growth Factor and Receptor Expression in Response to Altered Blood Flow In Vivo
,”
Circ. Res.
,
81
, pp.
320
327
.
18.
Pearson
,
J. D.
,
1994
, “
Endothelial Cell Function and Thrombosis
,”
Baillieres Clin. Haematol.
,
7
, pp.
441
452
.
19.
Longest, P. W., 2002, “Computational Analysis of Transient Particle Hemodynamics With Applications to Femoral Bypass Graft Designs,” Ph.D. Dissertation, Mechanical and Aerospace Engineering Department, North Carolina State University, Raleigh, NC.
20.
Longest
,
P. W.
, and
Kleinstreuer
,
C.
,
2003
, “
Comparison of Blood Particle Deposition Models for Non-Parallel Flow Domains
,”
J. Biomech.
,
36
, pp.
421
430
.
21.
Buchanan
,
J. R.
, and
Kleinstreuer
,
C.
,
1998
, “
Simulation of Particle Hemodynamics in a Partially Occluded Artery Segment With Implications to the Initiation of Microemboli and Secondary Stenoses
,”
J. Biomech. Eng.
,
120
, pp.
446
454
.
22.
Cokelet, G. R., 1987, The Rheology and Tube Flow of Blood. In: Handbook of Bioengineering, ed. R. Skalak and S. Chien, S., McGraw-Hill, New York, NY.
23.
Buchanan, J. R., 1996, “Computational Analysis of Particle Hemodynamics in Stenosed Artery Segments,” M.S. Thesis, Mechanical and Aerospace Engineering Department, North Carolina State University, Raleigh, NC.
24.
Bertschinger
,
K.
,
Cassina
,
P. C.
,
Debatin
,
J. F.
, and
Ruehm
,
S. G.
,
2001
, “
Surveillance of Peripheral Arterial Bypass Grafts With Three-Dimensional MR Angiography
,”
AJR, Am. J. Roentgenol.
,
176
, pp.
215
220
.
25.
Okadome
,
K.
,
Onohara
,
T.
,
Yamamura
,
S.
, and
Sugimachi
,
K.
,
1991
, “
Intraoperative Flow Waveform Analysis Aids in Preventing Early Graft Failure Following Reconstruction of Arteries of the Legs
,”
Ann. Vasc. Surg.
,
5
, pp.
413
418
.
26.
Buchanan, J. R., 2000, “Computational Particle Hemodynamics in the Rabbit Abdominal Aorta,” Ph.D. Dissertation, Mechanical and Aerospace Engineering Department, North Carolina State University, Raleigh, NC.
27.
Longest, P. W., Kleinstreuer, C., and Buchanan, J. R., 2003, “Efficient Computation of Micron-Particle Dynamics Including Wall Effects,” Comput. Fluids (in press).
28.
Loth
,
E.
,
2000
, “
Numerical Approaches for Motion of Dispersed Particles, Droplets and Bubbles
,”
Progress in Energy and Combustion Science
,
26
, pp.
161
223
.
29.
Kim, S., and Karrila, S. J., 1991, Microhydrodynamics: Principles and Selected Applications, Butterworth-Heinemann, Boston.
30.
Cherukat
,
P.
, and
McLaughlin
,
J. B.
,
1994
, “
The Inertial Lift on a Rigid Sphere in a Linear Shear Flow Field Near a Flat Wall
,”
J. Fluid Mech.
,
263
, pp.
1
18
.
31.
Aarts
,
P. A. M. M.
,
Steendijk
,
P.
,
Sixma
,
J. J.
, and
Heethaar
,
R. M.
,
1986
, “
Fluid Shear as a Possible Mechanism for Platelet Diffusivity in Flowing Blood
,”
J. Biomech.
,
19
(
10
), pp.
799
805
.
32.
Zydney
,
A. L.
, and
Colton
,
C. K.
,
1988
, “
Augmented Solute Transport in the Shear Flow of a Concentrated Suspension
,”
Physicochemical Hydrodynamics
,
10
, pp.
77
96
.
33.
Eckstein
,
E. C.
, and
Belgacem
,
F.
,
1991
, “
Model of Platelet Transport in Flowing Blood With Drift and Diffusion Terms
,”
Biophys. J.
,
60
, pp.
53
69
.
34.
Aarts
,
P. A.
,
van den Broek
,
S. A.
,
Prins
,
G. W.
,
Kuiken
,
G. D.
,
Sixma
,
J. J.
, and
Heethaar
,
R. M.
,
1988
, “
Blood Platelets are Concentrated Near the Wall and Red Blood Cells, in the Center of Flowing Blood
,”
Arteriosclerosis
,
8
(
6
), pp.
819
824
.
35.
Karino
,
T.
, and
Goldsmith
,
H. J.
,
1977
, “
Flow Behavior of Blood Cells and Rigid Spheres in an Annular Vortex
,”
Philos. Trans. R. Soc. London
,
279
, pp.
413
445
.
36.
Affeld
,
K.
,
Reininger
,
A. J.
,
Gadischke
,
J.
,
Grunert
,
K.
,
Schmidt
,
S.
, and
Thiele
,
F.
,
1995
, “
Fluid Mechanics of the Stagnation Point Flow Chamber and its Platelet Deposition
,”
Artif. Organs
,
19
(
7
), pp.
597
602
.
37.
Hinds
,
M. T.
,
Park
,
Y. J.
,
Jones
,
S. A.
,
Giddens
,
D. P.
, and
Alevriadou
,
B. R.
,
2001
, “
Local Hemodynamics Affect Monocytic Cell Adhesion to a Three-Dimensional Flow Model Coated With E-Selectin
,”
J. Biomech.
,
34
, pp.
95
103
.
38.
Goldsmith
,
H. L.
,
Frojmovic
,
M. M.
,
Braovac
,
S.
,
McIntosh
,
F.
, and
Wong
,
T.
,
1994
, “
Adenosine Diphosphate-Induced Aggregation of Human Platelets in Flow Through Tubes. III. Shear and Extrinsic Fibrinogen-Dependent Effects
,”
Thromb. Haemostasis
,
71
(
1
), pp.
78
90
.
39.
Hellums
,
J. D.
,
1994
, “
1993 Whitaker Lecture: Biorheology In Thrombosis Research
,”
Ann. Biomed. Eng.
,
22
(
5
), pp.
445
455
.
40.
Holme
,
P. A.
,
Orvim
,
U.
,
Hamers
,
M. J.
,
Solum
,
N. O.
, and
Brosstad
,
F. R.
,
1997
, “
Shear-Induced Platelet Activation and Platelet Microparticle Formation at Blood Flow Conditions as in Arteries With a Severe Stenosis
,”
Arterioscler., Thromb., Vasc. Biol.
,
17
(
4
), pp.
646
653
.
41.
Boreda
,
R.
,
Fatemi
,
R. S.
, and
Rittgers
,
S. E.
,
1995
, “
Potential for Platelet Stimulation in Critically Stenosed Carotid and Coronary Arteries
,”
J. Vasc. Investigation
,
1
(
1
), pp.
26
37
.
42.
Grabowski
,
E. F.
,
Reininger
,
A. J.
,
Petteruti
,
P. G.
,
Tsukurov
,
O.
, and
Orkin
,
R. W.
,
2001
, “
Shear Stress Decreases Endothelial Cell Tissue Factor Activity by Augmenting Secretion of Tissue Factor Pathway Inhibitor
,”
Arterioscler., Thromb., Vasc. Biol.
,
21
, pp.
157
162
.
43.
Grabowski
,
E. F.
,
Jaffe
,
E. A.
, and
Weksler
,
B. B.
,
1985
, “
Prostacyclin Production by Cultured Endothelial Cell Monolayers Exposed to Step Increase in Shear Stress
,”
J. Lab. Clin. Med.
,
105
, pp.
36
43
.
44.
Westmuckett
,
A. D.
,
Lupu
,
C.
,
Roquefeuil
,
S.
,
Krausz
,
T.
,
Kakkar
,
V. V.
, and
Lupu
,
F.
,
2000
, “
Fluid Flow Induces Up-Regulation of Synthesis and Release of Tissue Factor Pathway Inhibitor In Vitro
,”
Arterioscler., Thromb., Vasc. Biol.
,
20
, pp.
2474
2482
.
45.
Watase
,
M.
,
Kambayashi
,
J.
,
Itoh
,
T.
,
Tsuji
,
Y.
,
Kawasaki
,
T.
,
Shiba
,
E.
,
Sakon
,
M.
,
Mori
,
T.
,
Yashika
,
K.
, and
Hashimoto
,
P. H.
,
1992
, “
Ultrastructural Analysis of Pseudo-Intimal Hyperplasia of Polytetrafluoroethylene Prostheses Implanted Into the Venous and Arterial Systems
,”
Eur. J. Vasc. Surg.
,
6
, pp.
371
380
.
46.
Wootton
,
D. M.
, and
Ku
,
D. N.
,
1999
, “
Fluid Mechanics of Vascular Systems, Diseases, and Thrombosis
,”
Ann. Biomed. Eng.
,
10
, pp.
299
329
.
47.
Tambasco
,
M.
, and
Steinman
,
D. A.
,
2002
, “
On Assessing the Quality of Particle Tracking Through Computational Fluid Dynamic Models
,”
J. Biomech. Eng.
,
124
, pp.
166
175
.
48.
Longest
,
P. W.
, and
Kleinstreuer
,
C.
,
2000
, “
Computational Hemodynamics Analysis and Comparison Study of Arterio-Venous Grafts
,”
J. Med. Eng. Technol.
,
24
(
3
), pp.
102
110
.
49.
Ethier
,
C. R.
,
Steinman
,
D. A.
,
Zhang
,
X.
,
Karpik
,
S. R.
, and
Ojha
,
M.
,
1998
, “
Flow Waveform Effects on End-to-Side Anastomotic Flow Patterns
,”
J. Biomech.
,
31
, pp.
609
617
.
50.
Kleinstreuer
,
C.
,
Lei
,
M.
, and
Archie
,
J. P.
,
1996
, “
Flow Input Waveform Effects on the Temporal and Spatial Wall Shear Stress Gradients in a Femoral Graft-Artery Connector
,”
ASME J. Biomech. Eng.
,
118
, pp.
506
510
.
51.
Loth
,
F.
,
Jones
,
S.
,
Giddens
,
D.
,
Bassiouny
,
H.
,
Glagov
,
S.
, and
Zarins
,
C.
,
1997
, “
Measurements of Velocity and Wall Shear Stress Inside a PTFE Vascular Graft Model Under Steady Flow Conditions
,”
ASME J. Biomech. Eng.
,
119
, pp.
187
194
.
52.
Lei
,
M.
,
Kleinstreuer
,
C.
, and
Archie
,
J. P.
,
1997
, “
Hemodynamic Simulations and Computer-Aided Designs of Graft-Artery Junctions
,”
ASME J. Biomech. Eng.
,
119
, pp.
343
348
.
53.
Moore
,
J. A.
,
Steinman
,
D. A.
,
Prakash
,
S.
,
Johnston
,
K. W.
, and
Ethier
,
C. R.
,
1999
, “
A Numerical Study of Blood Flow Patterns in Anatomically Realistic and Simplified End-to-Side Anastomoses
,”
ASME J. Biomech. Eng.
,
121
, pp.
265
272
.
54.
Sharefkin
,
J. B.
,
Diamond
,
S. L.
,
Eskin
,
S. G.
,
McIntire
,
L. V.
, and
Diefenbach
,
C. W.
,
1991
, “
Fluid Flow Decreases Preproendothelin mRNA Levels and Suppresses Endothelin-1 Peptide Release in Cultured Human Endothelial Cells
,”
J. Vasc. Surg.
,
14
, pp.
1
9
.
55.
Ziats
,
N. P.
, and
Robertson
,
A. L.
,
1981
, “
Effects of Peripheral Blood Monocytes on Human Vascular Cell Proliferation
,”
Atherosclerosis
,
38
, pp.
401
410
.
56.
Ross
,
R.
,
1993
, “
The Pathogenesis of Atherosclerosis: A Perspective for the 1990s
,”
Nature (London)
,
362
, pp.
801
809
.
57.
Liu
,
S. Q.
,
1999
, “
Biomechanical Basis of Vascular Tissue Engineering
,”
Crit. Rev. Biomed. Eng.
,
27
(
1&2
), pp.
75
148
.
58.
Savage
,
B.
,
Saldivar
,
E.
, and
Ruggeri
,
Z. M.
,
1996
, “
Initiation of Platelet Adhesion by Arrest Onto Fibrinogen or Translocation on von Willebrand Factor
,”
Cell
,
84
(
2
), pp.
289
297
.
59.
Leu
,
H. J.
,
Feigl
,
W.
,
Susani
,
M.
, and
Odermatt
,
B.
,
1988
, “
Differentiation of Mononuclear Cells Into Macrophages, Fibroblasts, and Endothelial Cells in Thrombus Organization
,”
Exp. Cell Biol.
,
56
, pp.
201
210
.
60.
Sloope
,
G. D.
,
Fallon
,
K. B.
, and
Zieske
,
A. W.
,
2002
, “
Atherosclerotic Plaque-Like Lesions in Synthetic Arteriovenous Grafts: Implications for Atherogenesis
,”
Atherosclerosis
,
160
, pp.
133
139
.
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