The scar that forms after a myocardial infarction is often characterized by a highly disordered architecture but generally exhibits some degree of collagen fiber orientation, with a resulting mechanical anisotropy. When viewed in finer detail, however, the heterogeneity of the sample is clear, with different subregions exhibiting different fiber orientations. In this work, we used a multiscale finite element model to explore the consequences of the heterogeneity in terms of mechanical behavior. To do so, we used previously obtained fiber alignment maps of rat myocardial scar slices (n = 15) to generate scar-specific finite element meshes that were populated with fiber models based on the local alignment state. These models were then compared to isotropic models with the same sample shape and fiber density, and to homogeneous models with the same sample shape, fiber density, and average fiber alignment as the scar-specific models. All simulations involved equibiaxial extension of the sample with free motion in the third dimension. We found that heterogeneity led to a lower degree of mechanical anisotropy and a higher level of local stress concentration than the corresponding homogeneous model, and also that fibers failed in the heterogeneous model at much lower macroscopic strains than in the isotropic and homogeneous models. Taken together, these results suggest that scar heterogeneity may impair myocardial mechanical function both in terms of anisotropy and strength, and that individual variations in scar heterogeneity could be an important consideration for understanding scar remodeling and designing therapeutic interventions for patients after myocardial infarction.

References

References
1.
Benjamin
,
E.
,
Virani
,
S.
,
Callaway
,
C.
,
Chamberlain
,
A.
,
Chang
,
A.
,
Cheng
,
S.
,
Chiuve
,
S.
,
Cushman
,
M.
,
Delling
,
F.
,
Deo
,
R.
,
de Ferranti
,
S.
,
Ferguson
,
J.
,
Fornage
,
M.
,
Gillespie
,
C.
,
Isasi
,
C.
,
Jimenez
,
M.
,
Jordan
,
L.
,
Judd
,
S.
,
Lackland
,
D.
,
Lichtman
,
J.
,
Lisabeth
,
L.
,
Liu
,
S.
,
Longnecker
,
C.
,
Lutsey
,
P.
,
Mackey
,
J.
,
Matchar
,
D.
,
Matsushita
,
K.
,
Mussolino
,
M.
,
Nasir
,
K.
,
O'Flaherty
,
M.
,
Palaniappan
,
L.
,
Pandey
,
A.
,
Pandey
,
D.
,
Reeves
,
M.
,
Ritchey
,
M.
,
Rodrigues
,
C.
,
Roth
,
G.
,
Rosamond
,
W.
,
Sampson
,
U.
,
Satou
,
G.
,
Shah
,
S.
,
Spartano
,
N.
,
Tirschwell
,
D.
,
Tsao
,
C.
,
Jenifer
,
V.
,
Willey
,
J.
,
Wilkins
,
J.
,
Wu
,
J.
,
Alger
,
H.
,
Wong
,
S.
, and
Muntner
,
P.
,
2018
, “
Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association
,”
Circulation
,
137
(
12
), pp.
e67
e492
.
2.
Clarke
,
S. A.
,
Richardson
,
W. J.
, and
Holmes
,
J. W.
,
2016
, “
Modifying the Mechanics of Healing Infarcts: Is Better the Enemy of Good?
,”
J. Mol. Cell. Cardiol.
,
93
, pp.
115
124
.
3.
Richardson
,
W. J.
,
Clarke
,
S. A.
,
Alexander Quinn
,
T.
, and
Holmes
,
J. W.
,
2015
, “
Physiological Implications of Myocardial Scar Structure
,”
Compr. Physiol.
,
5
(
4
), pp.
1877
1909
.
4.
Jugdutt
,
B. I.
,
Joljart
,
M. J.
, and
Khan
,
M. I.
,
1996
, “
Rate of Collagen Deposition During Healing and Ventricular Remodeling After Myocardial Infarction in Rat and Dog Models
,”
Circulation
,
94
(
1
), pp.
94
101
.
5.
McCormick
,
R. J.
,
Musch
,
T. I.
,
Bergman
,
B. C.
, and
Thomas
,
D. P.
,
1994
, “
Regional Differences in LV Collagen Accumulation and Mature Cross-Linking After Myocardial Infarction in Rats
,”
Am. J. Physiol. Heart Circ. Physiol.
,
266
(
1
), pp.
H354
H359
.
6.
Zimmerman
,
S. D.
,
Thomas
,
D. P.
,
Velleman
,
S. G.
,
Li
,
X.
,
Hansen
,
T. R.
, and
McCormick
,
R. J.
,
2001
, “
Time Course of Collagen and Decorin Changes in Rat Cardiac and Skeletal Muscle Post-MI
,”
Am. J. Physiol. Heart Circ. Physiol.
,
281
(
4
), pp.
H1816
H1822
.
7.
Holmes
,
J. W.
,
Nuñez
,
J. A.
, and
Covell
,
J. W.
,
1997
, “
Functional Implications of Myocardial Scar Structure
,”
Am. J. Physiol.
,
272
(
5
), pp.
H2123
H2130
.
8.
Fomovsky
,
G. M.
,
Rouillard
,
A. D.
, and
Holmes
,
J. W.
,
2012
, “
Regional Mechanics Determine Collagen Fiber Structure in Healing Myocardial Infarcts
,”
J. Mol. Cell. Cardiol.
,
52
(
5
), pp.
1083
1090
.
9.
Fomovsky
,
G. M.
,
Clark
,
S. A.
,
Parker
,
K. M.
,
Ailawadi
,
G.
, and
Holmes
,
J. W.
,
2012
, “
Anisotropic Reinforcement of Acute Anteroapical Infarcts Improves Pump Function
,”
Circ. Heart Failure
,
5
(
4
), pp.
515
522
.
10.
Fomovsky
,
G. M.
, and
Holmes
,
J. W.
,
2010
, “
Evolution of Scar Structure, Mechanics, and Ventricular Function After Myocardial Infarction in the Rat
,”
Am. J. Physiol. Heart Circ. Physiol.
,
298
(
1
), pp.
H221
H228
.
11.
Richardson
,
W. J.
, and
Holmes
,
J. W.
,
2016
, “
Emergence of Collagen Orientation Heterogeneity in Healing Infarcts and an Agent-Based Model
,”
Biophys. J.
,
110
(
10
), pp.
2266
2277
.
12.
Joyce
,
E. M.
,
Liao
,
J.
,
Schoen
,
F. J.
,
Mayer
,
J. E.
, and
Sacks
,
M. S.
,
2009
, “
Functional Collagen Fiber Architecture of the Pulmonary Heart Valve Cusp
,”
Ann. Thorac. Surg.
,
87
(
4
), pp.
1240
1249
.
13.
Ban
,
E.
,
Zhang
,
S.
,
Zarei
,
V.
,
Barocas
,
V.
,
Winkelstein
,
B.
, and
Picu
,
C.
,
2017
, “
Collagen Organization in Facet Capsular Ligaments Varies With Spinal Region and With Ligament Deformation
,”
ASME J. Biomech. Eng.
,
139
(
7
), p.
071009
.
14.
Thomopoulos
,
S.
,
Williams
,
G. R.
,
Gimbel
,
J. A.
,
Favata
,
M.
, and
Soslowsky
,
L. J.
,
2003
, “
Variation of Biomechanical, Structural, and Compositional Properties Along the Tendon to Bone Insertion site
,”
J. Orthop. Res.
,
21
(
3
), pp.
413
419
.
15.
Hurks
,
R.
,
Pasterkamp
,
G.
,
Vink
,
A.
,
Hoefer
,
I. E.
,
Bots
,
M. L.
,
Van De Pavoordt
,
H. D.
,
De Vries
,
J. P. P.
, and
Moll
,
F. L.
,
2012
, “
Circumferential Heterogeneity in the Abdominal Aortic Aneurysm Wall Composition Suggests Lateral Sides to Be More Rupture Prone
,”
J. Vasc. Surg.
,
55
(
1
), pp.
203
209
.
16.
Gilling-Smith
,
G. L.
,
Vallabhaneni
,
S. R.
,
How
,
T. V.
,
Brennan
,
J. A.
,
Harris
,
P. L.
, and
Carter
,
S. D.
,
2005
, “
Heterogeneity of Tensile Strength and Matrix Metalloproteinase Activity in the Wall of Abdominal Aortic Aneurysms
,”
J. Endovascular Ther.
,
11
(
4
), pp.
494
502
.
17.
Witzenburg
,
C. M.
,
Dhume
,
R. Y.
,
Shah
,
S. B.
,
Korenczuk
,
C. E.
,
Wagner
,
H. P.
,
Alford
,
P. W.
, and
Barocas
,
V. H.
,
2017
, “
Failure of the Porcine Ascending Aorta: Multidirectional Experiments and a Unifying Model
,”
ASME J. Biomech. Eng.
,
139
(
3
), p.
031005
.
18.
Dhume
,
R. Y.
,
Shih
,
E. D.
, and
Barocas
,
V. H.
,
2019
, “
Multiscale Model of Fatigue of Collagen Gels
,”
Biomech. Model. Mechanobiol.
,
18
(
1
), pp.
175
187
.
19.
Zarei
,
V.
,
Liu
,
C. J.
,
Claeson
,
A. A.
,
Akkin
,
T.
, and
Barocas
,
V. H.
,
2017
, “
Image-Based Multiscale Mechanical Modeling Shows the Importance of Structural Heterogeneity in the Human Lumbar Facet Capsular Ligament
,”
Biomech. Model. Mechanobiol.
, 16(4), pp. 1425–1438.
20.
Jugdutt
,
B. I.
,
2003
, “
Ventricular Remodeling After Infarction and the Extracellular Collagen Matrix: When is Enough Enough?
,”
Circulation
,
108
(
11
), pp.
1395
1403
.
21.
Dewald
,
O.
,
Ren
,
G.
,
Duerr
,
G. D.
,
Zoerlein
,
M.
,
Klemm
,
C.
,
Gersch
,
C.
,
Tincey
,
S.
,
Michael
,
L. H.
,
Entman
,
M. L.
, and
Frangogiannis
,
N. G.
,
2004
, “
Of Mice and Dogs: Species-Specific Differences in the Inflammatory Response Following Myocardial Infarction
,”
Am. J. Pathol.
,
162
(
4
), pp.
665
677
.
22.
Fomovsky
,
G. M.
,
MacAdangdang
,
J. R.
,
Ailawadi
,
G.
, and
Holmes
,
J. W.
,
2011
, “
Model-Based Design of Mechanical Therapies for Myocardial Infarction
,”
J. Cardiovasc. Transl. Res.
,
4
(
1
), pp.
82
91
.
23.
Picu
,
R. C.
,
2011
, “
Mechanics of Random Fiber Networks—A Review
,”
Soft Matter
,
7
(
15
), pp.
6768
6785
.
24.
Hatami-Marbini
,
H.
, and
Picu
,
R. C.
,
2009
, “
Heterogeneous Long-Range Correlated Deformation of Semiflexible Random Fiber Networks
,”
Phys. Rev. E
,
80
(
4
), p.
046703
.
25.
Gao
,
X. M.
,
White
,
D. A.
,
Dart
,
A. M.
, and
Du
,
X. J.
,
2012
, “
Post-Infarct Cardiac Rupture: Recent Insights on Pathogenesis and Therapeutic Interventions
,”
Pharmacol. Ther.
,
134
(
2
), pp.
156
179
.
26.
Rouillard
,
A. D.
, and
Holmes
,
J. W.
,
2012
, “
Mechanical Regulation of Fibroblast Migration and Collagen Remodelling in Healing Myocardial Infarcts
,”
J. Physiol.
,
590
(
18
), pp.
4585
4602
.
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