Background: Intimal hyperplastic thickening (IHT) is a frequent cause of prosthetic bypass graft failure. Induction and progression of IHT is thought to involve a number of mechanisms related to variation in the flow field, injury and the prosthetic nature of the conduit. This study was designed to examine the relative contribution of wall shear stress and injury to the induction of IHT at defined regions of experimental end-to-side prosthetic anastomoses. Methods and Results: The distribution of IHT was determined at the distal end-to-side anastomosis of seven canine Iliofemoral PTFE grafts after 12 weeks of implantation. An upscaled transparent model was constructed using the in vivo anastomotic geometry, and wall shear stress was determined at 24 axial locations from laser Doppler anemometry measurements of the near wall velocity under conditions of pulsatile flow similar to that present in vivo. The distribution of IHT at the end-to-side PTFE graft was determined using computer assisted morphometry. IHT involving the native artery ranged from 0.0±0.1 mm to 0.05±0.03 mm. A greater amount of IHT was found on the graft hood (PTFE) and ranged from 0.09±0.06 to 0.24±0.06 mm. Nonlinear multivariable logistic analysis was used to model IHT as a function of the reciprocal of wall shear stress, distance from the suture line, and vascular conduit type (i.e. PTFE versus host artery). Vascular conduit type and distance from the suture line independently contributed to IHT. An inverse correlation between wall shear stress and IHT was found only for those regions located on the juxta-anastomotic PTFE graft. Conclusions: The data are consistent with a model of intimal thickening in which the intimal hyperplastic pannus migrating from the suture line was enhanced by reduced levels of wall shear stress at the PTFE graft/host artery interface. Such hemodynamic modulation of injury induced IHT was absent at the neighboring artery wall.

1.
Imparato
,
A. M.
,
Bracco
,
A.
,
Kim
,
G. E.
, and
Zeff
,
R.
,
1972
, “
Intimal and Neointimal Fibrous Proliferation Causing Failure of Arterial Reconstruction
,”
Surgery
,
72
, pp.
1007
1017
.
2.
Echave
,
V.
,
Koornick
,
A.
,
Haimov
,
M.
, and
Jacobson
,
J.
,
1979
, “
Intimal Hyperplasia as a Complication of the Use of the Polytetrafluoroethylene Graft for Femoral-Popliteal Bypass
,”
Surgery
,
86
, pp.
791
798
.
3.
Pedrini
,
L.
,
Pisano
,
E.
,
Donato
,
Di Paola M.
,
Balleste
,
A.
, and
Magnoni
,
F.
,
1994
, “
Late Occlusion of Aortofemoral Bypass Graft: Surgical Treatment
,”
Cardiovasc. Surg.
,
2
, pp.
763
766
.
4.
Zempo
,
N.
,
Esato
,
K.
,
O-Hara
,
M.
,
Fujioka
,
K.
,
Kuga
,
T.
, and
Takenaka
,
H.
,
1993
, “
Is the Preferential Use of Polytetrafluoroethylene Grafts for Below-Knee Femoropopliteal Bypass Justified?
Int. Surg.
,
78
, pp.
162
165
.
5.
Bryan
,
A. J.
, and
Angelini
,
G. D.
,
1994
, “
The Biology of Saphenous Vein Graft Occlusion: Etiology and Strategies for Prevention
,”
Curr. Opin. Cardiol.
,
9
, pp.
641
649
.
6.
Waller
,
B. F.
,
Pinkerton
,
C. A.
, and
Foster
,
L. N.
,
1987
, “
Morphologic Evidence of Accelerated Left Main Coronary Artery Stenosis: A Later Complication of Percutaneous Transluminal Balloon Angioplasty of the Proximal Left Anterior Descending Coronary Artery
,”
J. Am. Coll. Cardiol.
,
9
, pp.
1019
1023
.
7.
Liu
,
M. W.
,
Roubin
,
G. S.
, and
King
,
S. B.
,
1989
, “
Restenosis After Coronary Angioplasty: Potential Biologic Determinants and Role of Intimal Hyperplasia
,”
Circulation
,
79
, pp.
1374
1387
.
8.
Glagov
,
S.
,
1994
, “
Intimal Hyperplasia, Vascular Modeling and the Restenosis Problem
,”
Circulation
,
89
, pp.
2888
2891
.
9.
LoGerfo
,
F. W.
,
Soncrant
,
T.
,
Teel
,
T.
, and
Dewey
, Jr.,
C. F.
,
1979
, “
Boundary Layer Separation in Models of Side-to-End Arterial Anastomoses
,”
Archives of Surgery
,
114
, pp.
1369
1373
.
10.
Clark
,
R. E.
,
Apostolou
,
S.
, and
Kardos
,
J. L.
,
1976
, “
Mismatch of Mechanical Properties as a Cause of Arterial Prosthesis Thrombosis
,”
Surg. Forum
,
27
, pp.
208
210
.
11.
LoGerfo
,
F. W.
,
Quist
,
W. C.
,
Nowak
,
M. D.
,
Crawshaw
,
H. M.
, and
Haudenschild
,
C. C.
,
1983
, “
Downstream Anastomotic Hyperplasia. A Mechanism of Failure in Dacron Arterial Grafts
,”
Ann. Surgery
,
197
, pp.
479
483
.
12.
Clowes
,
A. W.
,
Gown
,
A. M.
,
Hanson
,
S. R.
, and
Reidy
,
M. A.
,
1985
, “
Mechanisms of Arterial Graft Failure, Role of Cellular Proliferation in Early Healing of PTFE Prostheses
,”
Am. J. Pathol.
,
118
, pp.
43
54
.
13.
Kamiya
,
A.
, and
Togawa
,
T.
,
1980
, “
Adaptive Regulation of Wall Shear Stress to Flow Change in the Canine Carotid Artery
,”
Am. J. Pathol.
,
239
, pp.
H14–H21
H14–H21
.
14.
Langille
,
B. L.
, and
O’Donnell
,
F.
,
1986
, “
Reductions in Arterial Diameter Produced by Chronic Decreases in Blood Flow are Endothelium-Dependent
,”
Science
,
231
, pp.
405
407
.
15.
Zarins
,
C. K.
,
Zatina
,
M. A.
,
Giddens
,
D. P.
,
Ku
,
D. N.
, and
Glagov
,
S.
,
1987
, “
Shear Stress Regulation of Artery Lumen Diameter in Experimental Atherogenesis
,”
J. Vasc. Surg.
,
5
, pp.
413
420
.
16.
Geary
,
R. L.
,
Kohler
,
T. R.
,
Vergel
,
S.
,
Kirkman
,
T. R.
, and
Clowes
,
A. W.
,
1994
, “
Time Course of Flow-Induced Smooth Muscle Cell Proliferation and Intimal Thickening in Endothelialized Baboon Vascular Grafts
,”
Circ. Res.
,
74
, pp.
14
23
.
17.
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.
,
24
, pp.
711
722
.
18.
Ojha
,
M.
,
Ethier
,
C. R.
,
Johnston
,
K. W.
, and
Cobbold
,
R. S.
,
1990
, “
Steady and Pulsatile Flow Fields in an End-to-Side Arterial Anastomosis Model
,”
J. Vasc. Surg.
,
12
, pp.
747
753
.
19.
Ojha
,
M.
,
1994
, “
Wall Shear Stress Temporal Gradient and Anastomotic Intimal Hyperplasia
,”
Circ. Res.
,
74
, pp.
1227
1231
.
20.
White
,
S. S.
,
Zarins
,
C. K.
,
Giddens
,
D. P.
,
Bassiouny
,
H. S.
,
Loth
,
F.
,
Jones
,
S. A.
, and
Glagov
,
S.
,
1993
, “
Hemodynamic Patterns in a Model of End-to-Side Vascular Graft Anastomoses: Effect of Pulsatility, Flow Division and Reynolds Number and Hood Length
,”
ASME J. Biomech. Eng.
,
115
, pp.
105
111
.
21.
Keynton
,
R.
,
Chapman
,
M. M.
,
Simms
,
R. L.
,
Rodway
,
N.
, and
Rittgers
,
S. E.
,
1995
, “
Direct Relationship between Wall Shear Rate and Intimal Hyperplasia in Vascular Bypass Grafts
,” ASME BED
Advances in Bioengineering
, Vol.
31
, pp.
169
170
.
22.
Bassiouny
,
H. S.
,
White
,
S.
,
Glagov
,
S.
,
Choi
,
E.
,
Giddens
,
D. P.
, and
Zarins
,
C. K.
,
1991
, “
Anastomotic Intimal Hyperplasia: Mechanical Injury or Flow Induced
,”
J. Vasc. Surg.
,
15
, pp.
708
717
.
23.
Bassiouny
,
H. S.
,
Krievins
,
D.
,
Glagov
,
S.
,
Abu-hamid
,
G.
, and
Zarins
,
C. K.
,
1993
, “
Distal Arteriovenous Fistula Inhibits Experimental Anastomotic Intimal Thickening
,”
Surg. Forum
,
XLIV
, pp.
345
346
.
24.
Giddens, E. M., Giddens, D. P., White, S. S., Zarins, C. K., Bassiouny, H. S., and Glagov, S., 1993, “Exercise Flow Conditions Eliminate Stasis at Vascular Graft Anastomoses,” Proceedings of the Third Mid-Atlantic Conference in Biofluid Mechanics, pp. 255–267.
25.
Bassiouny, H. S., Ng, A., and Glagov, S., “Low Shear Stress Enhances Progression of Anastomotic Intimal Hyperplasia,” Submitted to Ann. Vasc. Surg.
26.
Cleary, J. P., and Levenbach, H., 1982, The Professional Forecaster: The Forecasting Process Through Data Analysis, Lifetime Learning Publications, Belmont, Ca.
27.
Loth, F., 1993, “Velocity and Wall Shear Measurements Inside a Vascular Graft Model Under Steady and Pulsatile Flow Conditions,” Ph.D. Thesis, Georgia Institute of Technology, Atlanta, GA.
28.
Loth
,
F.
,
Jones
,
S. A.
,
Giddens
,
D. P.
,
Bassiouny
,
H. S.
,
Zarins
,
C. K.
, and
Glagov
,
S.
,
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
.
29.
Loth, F., Jones, S. A., Giddens, D. P., and Brossollet, L. J., 1994, “Accuracy of Wall Shear Stress Estimates from Laser Doppler Anemometry Measurements Under Unsteady Flow Conditions,” Advances in Bioengineering, Proceedings of the ASME Winter Annual Meeting, pp. 307–308.
30.
Ku
,
D. N.
,
Giddens
,
D. P.
,
Zarins
,
C. K.
, and
Glagov
,
S.
,
1985
, “
Pulsatile Flow and Atherosclerosis in the Human Carotid Bifurcation: Positive Correlation Between Plaque Location and Low and Oscillating Shear Stress
,”
Arteriosclerosis
5
, pp.
293
302
.
31.
Glagov, S., and Zarins, C. K., 1983, “Quantitating Atherosclerosis; Problems of Definition in Clinical Diagnosis,” Clinical Diagnosis of Atherosclerosis Quantitative Methods of Evaluation, M. Bond et al., eds., Springer-Verlag, New York, pp. 11–35.
32.
Zarins
,
C. K.
,
Giddens
,
D. P.
,
Bharadvaj
,
B. K.
,
Sottiurai
,
V. S.
,
Mabon
,
R. F.
, and
Glagov
,
S.
,
1983
, “
Carotid Bifurcation Atherosclerosis: Quantitative Correlation of Plaque Localization With Flow Velocity Profiles and Wall Shear Stress
,”
Circ. Res.
,
53
, pp.
502
514
.
33.
Bharadvaj
,
B. K.
,
Mabon
,
R. F.
, and
Giddens
,
D. P.
,
1982
, “
Steady Flow in a Model of the Human Carotid Bifurcation: I. Flow Visualization
,”
ASME J. Biomech. Eng.
,
15
, pp.
348
362
.
34.
Svindland
,
A.
,
1983
, “
The Localization of Subanophilie and Fibrous Plaques in the Main Left Coronary Arteries
,”
Atherosclerosis
48
, pp.
139
145
.
35.
Fox
,
B.
,
James
,
K.
,
Morgan
,
B.
, and
Seed
,
A.
,
1982
, “
Distribution of Fatty and Fibrous Plaques in Young Human Coronary Arteries
,”
Atherosclerosis
41
, pp.
337
347
.
36.
Sabbah
,
H. N.
,
Khaja
,
F.
,
Brymer
,
J. F.
,
Hawkins
,
E. T.
, and
Stein
,
P. D.
,
1984
, “
Blood Velocity in the Right Coronary Artery: Relation to the Distribution of Atherosclerotic Lesions
,”
Am. J. Cardiol.
,
53
, pp.
1008
1012
.
37.
Friedman
,
M. H.
,
Bargeron
,
C. B.
,
Deters
,
O. J.
,
Hutchins
,
G. M.
, and
Mark
,
F. F.
,
1987
, “
Correlation Between Wall Shear and Intimal Thickness at a Coronary Artery Branch
,”
Atherosclerosis
68
, pp.
27
33
.
38.
Tang, T., 1990, “Periodic Flow in a Bifurcating Tube at Moderate Reynolds Number,” Ph.D. Thesis, Georgia Institute of Technology, Atlanta, GA.
39.
Asakura
,
T.
, and
Karino
,
T.
,
1990
, “
Flow Patterns and Spatial Distribution of Atherosclerotic Lesions in Human Coronary Arteries
,”
Circ. Res.
,
66
, pp.
1045
66
.
40.
Krams
,
R.
,
Wentzel
,
J. J.
,
Oomen
,
J. A. F.
,
Vinke
,
R.
,
Schuurbiers
,
J. C. H.
,
Feyter
,
P. J.
,
Serruys
,
P. W.
, and
Stager
,
C. J.
,
1997
, “
Evaluation of Endothelial Shear Stress and 3D Geometry as Factors Determining the Development of Atherosclerosis and Remodeling in Human Coronary Arteries in Vitro, Combining 3D Reconstruction from Angiography and IVUS (ANGUS) With Computational Fluid Dynamics
,”
Arterioscler., Thromb., Vasc. Biol.
,
17
, pp.
2061
2065
.
41.
Moore
, Jr.,
J. E.
,
Xu
,
C.
,
Glagov
,
S.
,
Zarins
,
C. K.
, and
Ku
,
D. N.
,
1994
, “
Fluid Wall Shear Stress Measurements in a Model of the Human Abdominal Aorta; Oscillatory behavior and relationship to Atherosclerosis
,”
Atherosclerosis
110
, pp.
225
240
.
42.
Papadaki
,
M.
,
McIntire
,
L. V.
, and
Eskin
,
S. G.
,
1996
, “
Effects of Shear Stress on the Growth Kinetics of Human Aortic Smooth Muscle Cells in Vitro
,”
Biotechnol. Bioeng.
,
50
, pp.
555
561
.
43.
Alshihabi
,
S. N.
,
Chang
,
Y. S.
,
Frangos
,
J. A.
, and
Tarbell
,
J. M.
,
1996
, “
Shear Stress-Induced Release of PGE2 and PGI2 by Vascular Smooth Muscle Cells
,”
Biochem. Biophys. Res. Commun.
,
224
, pp.
808
814
.
44.
Gadson
, Jr.,
P. F.
,
Rossignol
,
C.
,
McCoy
,
J.
, and
Rosenquist
,
T. H.
,
1993
, “
Expression of Elastin, Smooth Muscle Alpha-Actin, and C-Jun as a Function of the Embryonic Lineage of Vascular Smooth Muscle Cells
,”
In Vitro Cell. Dev. Biol.: Anim.
,
29A
, pp.
773
781
.
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