The engineering foundation for novel approaches for the repair of congenital defects that involve the main pulmonary artery (PA) must rest on an understanding of changes in the structure-function relationship that occur during postnatal maturation. In the present study, we quantified the postnatal growth patterns in structural and biomechanical behavior in the ovine PA in the juvenile and adult stages. The biaxial mechanical properties and collagen and elastin fiber architecture were studied in four regions of the PA wall, with the collagen recruitment of the medial region analyzed using a custom biaxial mechanical-multiphoton microscopy system. Circumferential residual strain was also quantified at the sinotubular junction and bifurcation locations, which delimit the PA. The PA wall demonstrated significant mechanical anisotropy, except in the posterior region where it was nearly isotropic. Overall, we observed only moderate changes in regional mechanical properties with growth. We did observe that the medial and lateral locations experience a moderate increase in anisotropy. There was an average of about 24% circumferential residual stain present at the luminal surface in the juvenile stage that decreased to 16% in the adult stage with a significant decrease at the bifurcation, implying that the PA wall remodels toward the bifurcation with growth. There were no measurable changes in collagen and elastin content of the tunica media with growth. On average, the collagen fiber recruited more rapidly with strain in the adult compared to the juvenile. Interestingly, the PA thickness remained constant with growth. When this fact is combined with the observed stable overall mechanical behavior and increase in vessel diameter with growth, a simple Laplace Law wall stress estimate suggests an increase in effective PA wall stress with postnatal maturation. This observation is contrary to the accepted theory of maintenance of homeostatic stress levels in the regulation of vascular function and suggests alternative mechanisms regulate postnatal somatic growth. Understanding the underlying mechanisms, incorporating important structural features during growth, will help to improve our understanding of congenital defects of the PA and lay the basis for functional duplication in their repair and replacement.

References

References
1.
Adatia
,
I.
,
Kothari
,
S. S.
, and
Feinstein
,
J. A.
,
2010
, “
Pulmonary Hypertension Associated With Congenital Heart Disease: Pulmonary Vascular Disease: The Global Perspective
,”
Chest
,
137
(
6 Suppl
), pp.
52S
61S
.10.1378/chest.09-2861
2.
Tulloh
,
R. M.
,
2005
, “
Congenital Heart Disease in Relation to Pulmonary Hypertension in Paediatric Practice
,”
Paediatr. Respir. Rev.
,
6
(
3
), pp.
174
180
.10.1016/j.prrv.2005.06.010
3.
Deterling
,
R. A.
, Jr.
, and
Clagett
,
O. T.
,
1947
, “
Aneurysm of the Pulmonary Artery: Review of the Literature and Report of a Case
,”
Am. Heart J.
,
34
(
4
), pp.
471
499
.10.1016/0002-8703(47)90527-9
4.
Kutty
,
S.
,
Kaul
,
S.
,
Danford
,
C. J.
, and
Danford
,
D. A.
,
2010
, “
Main Pulmonary Artery Dilation in Association with Congenital Bicuspid Aortic Valve in the Absence of Pulmonary Valve Abnormality
,”
Heart
,
96
(
21
), pp.
1756
1761
.10.1136/hrt.2010.199109
5.
Patnaik
,
A. N.
,
Barik
,
R.
,
Babu
,
S.
, and
Gullati
,
A. S.
,
2012
, “
A Rare Case of Left Lung Hypoplasia Associated With Congenital Pulmonary Artery Aneurysm and Ventricular Septal Defect
,”
Pediatr. Cardiol.
(in press).
6.
Greenwald
,
S. E.
,
Johnson
,
R. J.
, and
Haworth
,
S. G.
,
1984
, “
Pulmonary Vascular Input Impedance in the Newborn and Infant Pig
,”
Cardiovasc. Res.
,
18
, pp.
44
50
.10.1093/cvr/18.1.44
7.
Lammers
,
S. R.
,
Kao
,
P. H.
,
Qi
,
H. J.
,
Hunter
,
K.
,
Lanning
,
C.
,
Albietz
,
J.
,
Hofmeister
,
S.
,
Mecham
,
R.
,
Stenmark
,
K. R.
, and
Shandas
,
R.
,
2008
, “
Changes in the Structure-Function Relationship of Elastin and Its Impact on the Proximal Pulmonary Arterial Mechanics of Hypertensive Calves
,”
Am. J. Physiol. Heart Circ. Physiol.
,
295
(
4
), pp.
H1451
H1459
.10.1152/ajpheart.00127.2008
8.
Kogon
,
B. E.
,
Patel
,
M.
,
Pernetz
,
M.
,
Mcconnell
,
M.
, and
Book
,
W.
,
2009
, “
Late Pulmonary Valve Replacement in Congenital Heart Disease Patients Without Original Congenital Pulmonary Valve Pathology
,”
Pediatr. Cardiol.
,
31
(
1
), pp.
74
79
.10.1007/s00246-009-9574-3
9.
Ono
,
M.
,
Goerler
,
H.
,
Kallenbach
,
K.
,
Boethig
,
D.
,
Westhoff-Bleck
,
M.
, and
Breymann
,
T.
,
2007
, “
Aortic Valve-Sparing Reimplantation for Dilatation of the Ascending Aorta and Aortic Regurgitation Late After Repair of Congenital Heart Disease
,”
J. Thorac. Cardiovasc. Surg.
,
133
(
4
), pp.
876
879
.10.1016/j.jtcvs.2006.10.055
10.
Rosenberg
,
H. G.
,
Williams
,
W. G.
,
Trusler
,
G. A.
,
Higa
,
T.
, and
Rabinovitch
,
M.
,
1987
, “
Structural Composition of Central Pulmonary Arteries. Growth Potential After Surgical Shunts
,”
J. Thorac. Cardiovasc. Surg.
,
94
(
4
), pp.
498
503
.
11.
Mayer
,
J. E.
, Jr
.,
1995
, “
Uses of Homograft Conduits for Right Ventricle to Pulmonary Artery Connections in the Neonatal Period
,”
Semin. Thorac. Cardiovasc. Surg.
,
7
(
3
), pp.
130
132
.
12.
Cho
,
S. W.
,
Kim
,
I. K.
,
Kang
,
J. M.
,
Song
,
K. W.
,
Kim
,
H. S.
,
Park
,
C. H.
,
Yoo
,
K. J.
, and
Kim
,
B. S.
,
2009
, “
Evidence for In Vivo Growth Potential and Vascular Remodeling of Tissue-Engineered Artery
,”
Tissue Eng. Part A
,
15
(
4
), pp.
901
912
.10.1089/ten.tea.2008.0172
13.
Hoerstrup
,
S. P.
,
Cummings Mrcs
,
I.
,
Lachat
,
M.
,
Schoen
,
F. J.
,
Jenni
,
R.
,
Leschka
,
S.
,
Neuenschwander
,
S.
,
Schmidt
,
D.
,
Mol
,
A.
,
Gunter
,
C.
,
Gossi
,
M.
,
Genoni
,
M.
, and
Zund
,
G.
,
2006
, “
Functional Growth in Tissue-Engineered Living, Vascular Grafts: Follow-up at 100 Weeks in a Large Animal Model
,”
Circulation
,
114
(
1 Suppl
), pp.
I159
I166
.10.1161/CIRCULATIONAHA.105.001172
14.
Shinoka
,
T.
,
Shum-Tim
,
D.
,
Ma
,
P. X.
,
Tanel
,
R. E.
,
Isogai
,
N.
,
Langer
,
R.
,
Vacanti
,
J. P.
, and
Mayer
,
J. E.
, Jr
.,
1998
, “
Creation of Viable Pulmonary Artery Autografts Through Tissue Engineering
,”
J. Thorac. Cardiovasc. Surg.
,
115
(
3
), pp.
536
546
.10.1016/S0022-5223(98)70315-0
15.
Mol
,
A.
,
Smits
,
A. I.
,
Bouten
,
C. V.
, and
Baaijens
,
F. P.
,
2009
, “
Tissue Engineering of Heart Valves: Advances and Current Challenges
,”
Expert Rev. Med. Devices
,
6
(
3
), pp.
259
275
.10.1586/erd.09.12
16.
Huang
,
Y.
,
Guo
,
X.
, and
Kassab
,
G. S.
,
2006
, “
Axial Nonuniformity of Geometric and Mechanical Properties of Mouse Aorta is Increased During Postnatal Growth
,”
Am. J. Physiol. Heart Circ. Physiol.
,
290
(
2
), pp.
H657
H664
.10.1152/ajpheart.00803.2005
17.
Sugimoto
,
T.
,
Miyazaki
,
H.
, and
Hayashi
,
K.
,
2003
, “
Age-Related Changes in the Morphology and Mechanics of Arterial Wall in the Rat
,”
JSME Int. J.
,
46
(
4
), pp.
1312
1320
.10.1299/jsmec.46.1312
18.
Wells
,
S. M.
,
Langille
,
B. L.
, and
Adamson
,
S. L.
,
1998
, “
In Vivo and In Vitro Mechanical Properties of the Sheep Thoracic Aorta in the Perinatal Period and Adulthood
,”
Am. J. Physiol.
,
274
(
43
), pp.
H1749
H1760
.
19.
Wells
,
S. M.
,
Langille
,
B. L.
,
Lee
,
J. M.
, and
Adamson
,
S. L.
,
1999
, “
Determinants of Mechanical Properties in the Developing Ovine Thoracic Aorta
,”
Am. J. Physiol.
,
277
(
4
), pp.
H1385
H1391
.
20.
Haskett
,
D.
,
Johnson
,
G.
,
Zhou
,
A.
,
Utzinger
,
U.
, and
Vande Geest
,
J.
,
2010
, “
Microstructural and Biomechanical Alterations of the Human Aorta as a Function of Age and Location
,”
Biomech. Model. Mechanobiol.
,
9
(
6
), pp.
725
736
.10.1007/s10237-010-0209-7
21.
Bruel
,
A.
, and
Oxlund
,
H.
,
1996
, “
Changes in Biomechanical Properties, Composition of Collagen and Elastin, and Advanced Glycation Endproducts of the Rat Aorta in Relation to Age
,”
Atherosclerosis
,
127
(
2
), pp.
155
165
.10.1016/S0021-9150(96)05947-3
22.
Gaballa
,
M. A.
,
Jacob
,
C. T.
,
Raya
,
T. E.
,
Liu
,
J.
,
Simon
,
B.
, and
Goldman
,
S.
,
1998
, “
Large Artery Remodeling During Aging: Biaxial Passive and Active Stiffness
,”
Hypertension
,
32
(
3
), pp.
437
443
.10.1161/01.HYP.32.3.437
23.
Boumaza
,
S.
,
Arribas
,
S. M.
,
Osborne-Pellegrin
,
M.
,
Mcgrath
,
J. C.
,
Laurent
,
S.
,
Lacolley
,
P.
, and
Challande
,
P.
,
2001
, “
Fenestrations of the Carotid Internal Elastic Lamina and Structural Adaptation in Stroke-Prone Spontaneously Hypertensive Rats
,”
Hypertension
,
37
(
4
), pp.
1101
1107
.10.1161/01.HYP.37.4.1101
24.
Gottlieb
,
D.
,
Kunal
,
T.
,
Emani
,
S.
,
Aikawa
,
E.
,
Brown
,
D. W.
,
Powell
,
A. J.
,
Nedder
,
A.
,
Engelmayr
,
G. C.
, Jr.
,
Melero-Martin
,
J. M.
,
Sacks
,
M. S.
, and
Mayer
,
J. E.
, Jr.
,
2010
, “
In Vivo Monitoring of Function of Autologous Engineered Pulmonary Valve
,”
J. Thorac. Cardiovasc. Surg.
,
139
(
3
), pp.
723
731
.10.1016/j.jtcvs.2009.11.006
25.
Gottlieb
,
D.
,
Fata
,
B.
,
Powell
,
A. J.
,
Cois
,
A.
,
Annese
,
D.
,
Tandon
,
K.
,
Stetten
,
G.
,
Mayer
,
J. E.
, Jr.
, and
Sacks
,
M. S.
, “
Pulmonary Artery Dimensional Changes in a Growing Ovine Model: Comparisons With the Ascending Aorta
,”
J. Heart Valve Dis.
(in-press).
26.
Fata
,
B.
,
Gottlieb
,
D.
,
Mayer
,
J. E.
, and
Sacks
,
M. S.
, “
Postnatal In Vivo Surface Growth Deformation Patterns of the Ovine Main Pulmonary Artery and Ascending Aorta
,”
J. Biomech. Eng.
(submitted).
27.
Grashow
,
J.
,
2005
, “
Evaluation of the Biaxial Mechanical Properties of the Mitral Valve Leaflet Under Physiological Loading Conditions
,” Ph.D. thesis, University of Pittsburgh, Pittsburgh, PA.
28.
Han
,
H. C.
, and
Fung
,
Y. C.
,
1996
, “
Direct Measurement of Transverse Residual Strains in Aorta
,”
Am. J. Physiol.
,
270
(
2 Pt 2
), pp.
H750
H759
.
29.
Meijering
,
E.
,
Jacob
,
M.
,
Sarria
,
J. C. F.
,
Steiner
,
P.
,
Hirling
,
H.
, and
Unser
,
M.
,
2004
, “
Design and Validation of a Tool for Neurite Tracing and Analysis in Fluorescence Microscopy Images
,”
Cytometry
, Part A,
58A
(
2
), pp.
167
176
.10.1002/cyto.a.20022
30.
Hill
,
M. R.
,
Duan
,
X.
,
Gibson
,
G. A.
,
Watkins
,
S.
, and
Robertson
,
A. M.
,
2012
, “
A Theoretical and Non-Destructive Experimental Approach for Direct Inclusion of Collagen Orientaiton and Recruitment Into Mechanical Models of the Artery Wall
,”
J. Biomech.
,
45
(
5
), pp.
762
771
.10.1016/j.jbiomech.2011.11.016
31.
Courtney
,
T.
,
Sacks
,
M. S.
,
Stankus
,
J.
,
Guan
,
J.
, and
Wagner
,
W. R.
,
2006
, “
Design and Analysis of Tissue Engineering Scaffolds That Mimic Soft Tissue Mechanical Anisotropy
,”
Biomaterials
,
27
(
19
), pp.
3631
3638
.10.1016/j.biomaterials.2006.02.024
32.
Vande Geest
,
J. P.
,
Di Martino
,
E. S.
,
Bohra
,
A.
,
Makaroun
,
M. S.
, and
Vorp
,
D. A.
,
2006
, “
A Biomechanics-Based Rupture Potential Index for Abdominal Aortic Aneurysm Risk Assessment: Demonstrative Application
,”
Ann. N. Y. Acad. Sci.
,
1085
, pp.
11
21
.10.1196/annals.1383.046
33.
Gozna
,
E. R.
,
Marble
,
A. E.
,
Shaw
,
A.
, and
Holland
,
J. G.
,
1974
, “
Age-Related Changes in the Machanics of the Aorta and Pulmonary Artery of Man
,”
J. Appl. Physiol.
,
36
(
4
), pp.
407
411
.
34.
Vande Geest
,
J. P.
,
Sacks
,
M. S.
, and
Vorp
,
D. A.
,
2004
, “
Age Dependency of the Biaxial Biomechanical Behavior of Human Abdominal Aorta
,”
J. Biomech. Eng.
,
126
(
6
), pp.
815
822
.10.1115/1.1824121
35.
Choudhury
,
N.
,
Bouchot
,
O.
,
Rouleau
,
L.
,
Tremblay
,
D.
,
Cartier
,
R.
,
Butany
,
J.
,
Mongrain
,
R.
, and
Leask
,
R. L.
,
2009
, “
Local Mechanical and Structural Properties of Healthy and Diseased Human Ascending Aorta Tissue
,”
Cardiovasc. Pathol.
,
18
(
2
), pp.
83
91
.10.1016/j.carpath.2008.01.001
36.
Patel
,
D. J.
,
Schilder
,
D. P.
, and
Mallos
,
A. J.
,
1960
, “
Mechanical Properties and Dimensions of the Major Pulmonary Arteries
,”
J. Appl. Physiol.
,
15
(
1
), pp.
92
96
.
37.
Drexler
,
E. S.
,
Quinn
,
T. P.
,
Slifka
,
A. J.
,
Mccowan
,
C. N.
,
Bischoff
,
J. E.
,
Wright
,
J. E.
,
Ivy
,
D. D.
, and
Shandas
,
R.
,
2007
, “
Comparison of Mechanical Behavior Among the Extrapulmonary Arteries from Rats
,”
J. Biomech.
,
40
(
4
), pp.
812
819
.10.1016/j.jbiomech.2006.03.010
38.
Hunter
,
K. S.
,
Albietz
,
J. A.
,
Lee
,
P. F.
,
Lanning
,
C. J.
,
Lammers
,
S. R.
,
Hofmeister
,
S. H.
,
Kao
,
P. H.
,
Qi
,
H. J.
,
Stenmark
,
K. R.
, and
Shandas
,
R.
,
2010
, “
In Vivo Measurement of Proximal Pulmonary Artery Elastic Modulus in the Neonatal Calf Model of Pulmonary Hypertension: Development and Ex Vivo Validation
,”
J. Appl. Physiol.
,
108
(
4
), pp.
968
975
.10.1152/japplphysiol.01173.2009
39.
Chesler
,
N. C.
,
Thompson-Figueroa
,
J.
, and
Millburne
,
K.
,
2004
, “
Measurements of Mouse Pulmonary Artery Biomechanics
,”
J. Biomech. Eng.
,
126
(
2
), pp.
309
314
.10.1115/1.1695578
40.
Patel
,
D. J.
,
Freitas
,
F. M. D.
, and
Mallos
,
A. J.
,
1962
, “
Mechanical Function of the Main Pulmonary Artery
,”
J. Appl. Physiol.
,
17
(
2
), pp.
205
208
.
41.
Chuong
,
C. J.
, and
Fung
,
Y. C.
,
1986
, “
On Residual Stress in Arteries
,”
J. Biomech. Eng.
,
108
, pp.
189
192
.10.1115/1.3138600
42.
Fung
,
Y. C.
,
1990
,
Biomechanics: Motion, Flow, Stress, and Growth
,
Springer
,
New York
, p.
569
.
43.
Vaishnav
,
R. N.
, and
Vossoughi
,
J.
,
1983
, “
Estimation of Residual Strains in Aortic Segments
,”
Biomechanical Engineering II, Recent Developments
,
Pergamon
,
New York
, pp.
330
333
.
44.
Jiang
,
Z. L.
,
Kassab
,
G. S.
, and
Fung
,
Y. C.
,
1994
, “
Diameter-Defined Strahler System and Connectivity Matrix of the Pulmonary Arterial Tree
,”
J. Appl. Physiol.
,
76
(
2
), pp.
882
892
.
45.
Fung
,
Y. C.
,
1991
, “
What Are the Residual Stresses Doing in Our Blood Vessels?
,”
Ann. Biomed. Eng.
,
19
(
3
), pp.
237
249
.10.1007/BF02584301
46.
Liu
,
S. Q.
, and
Fung
,
Y. C.
,
1992
, “
Changes in the Rheological Properties of Blood Vessel Tissue Remodeling in the Course of Development of Diabetes
,”
Biorheology
,
29
(
5-6
), pp.
443
457
.
47.
Zou
,
Y.
, and
Zhang
,
Y.
,
2009
, “
An Experimental and Theoretical Study on the Anisotropy of Elastin Network
,”
Ann. Biomed. Eng.
,
37
(
8
), pp.
1572
1583
.10.1007/s10439-009-9724-z
48.
Lillie
,
M. A.
,
Shadwick
,
R. E.
, and
Gosline
,
J. M.
,
2010
, “
Mechanical Anisotropy of Inflated Elastic Tissue From the Pig Aorta
,”
J. Biomech.
,
43
(
11
), pp.
2070
2078
.10.1016/j.jbiomech.2010.04.014
49.
Roach
,
M. R.
, and
Burton
,
A. C.
,
1957
, “
The Reason for the Shape of the Distensibility Curves of Arteries
,”
Can. J. Biochem. Physiol.
,
35
, pp.
681
690
.10.1139/o57-080
50.
Hill
,
M.
,
2011
, “
A Novel Approach for Combining Biomechanical and Micro-Structural Analyses to Assess the Mechanical and Damage Properties of the Artery Wall
,” Ph.D. thesis, University of Pittsburgh, Pittsburgh, PA.
51.
Keyes
,
J. T.
,
Lockwood
,
D. R.
,
Utzinger
,
U.
,
Montilla
,
L. G.
,
Witte
,
R. S.
, and
Vande Geest
,
J. P.
,
2012
, “
Comparisons of Planar and Tubular Biaxial Tensile Testing Protocols of the Same Porcine Coronary Arteries
,”
Ann. Biomed. Eng.
(in press).
52.
Keyes
,
J. T.
,
Haskett
,
D. G.
,
Utzinger
,
U.
,
Azhar
,
M.
, and
Vande Geest
,
J. P.
,
2011
, “
Adaptation of a Planar Microbiaxial Optomechanical Device for the Tubular Biaxial Microstructural and Macroscopic Characterization of Small Vascular Tissues
,”
J. Biomech. Eng.
,
133
(
7
), p.
075001
.10.1115/1.4004495
53.
Hollander
,
Y.
,
Durban
,
D.
,
Lu
,
X.
,
Kassab
,
G. S.
, and
Lanir
,
Y.
,
2011
, “
Experimentally Validated Microstructural 3d Constitutive Model of Coronary Arterial Media
,”
J. Biomech. Eng.
,
133
(
3
), p.
031007
.10.1115/1.4003324
54.
Hollander
,
Y.
,
Durban
,
D.
,
Lu
,
X.
,
Kassab
,
G. S.
, and
Lanir
,
Y.
,
2011
, “
Constitutive Modeling of Coronary Arterial Media–Comparison of Three Model Classes
,”
J. Biomech. Eng.
,
133
(
6
), p.
061008
.10.1115/1.4004249
55.
Freed
,
A. D.
, and
Doehring
,
T. C.
,
2005
, “
Elastic Model for Crimped Collagen Fibrils
,”
J. Biomech. Eng.
,
127
(
4
), pp.
587
593
.10.1115/1.1934145
56.
Prot
,
V.
,
Skallerud
,
B.
,
Sommer
,
G.
, and
Holzapfel
,
G. A.
,
2010
, “
On Modelling and Analysis of Healthy and Pathological Human Mitral Valves: Two Case Studies
,”
J. Mech. Behav. Biomed. Mater.
,
3
(
2
), pp.
167
177
.10.1016/j.jmbbm.2009.05.004
57.
Ooi
,
C. Y.
,
Wang
,
Z.
,
Tabima
,
D. M.
,
Eickhoff
,
J. C.
, and
Chesler
,
N. C.
,
2010
, “
The Role of Collagen in Extralobar Pulmonary Artery Stiffening in Response to Hypoxia-Induced Pulmonary Hypertension
,”
Am. J. Physiol. Heart Circ. Physiol.
,
299
(
6
), pp.
H1823
H1831
.10.1152/ajpheart.00493.2009
58.
Tozzi
,
C. A.
,
Christiansen
,
D. L.
,
Poiani
,
G. J.
, and
Riley
,
D. J.
,
1994
, “
Excess Collagen in Hypertensive Pulmonary Arteries Decreases Vascular Distensibility
,”
Am. J. Respir. Crit. Care Med.
,
149
(
5
), pp.
1317
1326
.
59.
Poiani
,
G. J.
,
Tozzi
,
C. A.
,
Yohn
,
S. E.
,
Pierce
,
R. A.
,
Belsky
,
S. A.
,
Berg
,
R. A.
,
Yu
,
S. Y.
,
Deak
,
S. B.
, and
Riley
,
D. J.
,
1990
, “
Collagen and Elastin Metabolism in Hypertensive Pulmonary Arteries of Rats
,”
Circ. Res.
,
66
(
4
), pp.
968
978
.10.1161/01.RES.66.4.968
60.
Berry
,
C. L.
,
Looker
,
T.
, and
Germain
,
J.
,
1972
, “
The Growth and Development of the Rat Aorta. I. Morphological Aspects
,”
J. Anat.
,
113
(
Pt 1
), pp.
1
16
.
61.
Leung
,
D. Y. M.
,
Glagov
,
S.
, and
Mathews
,
M. B.
,
1977
, “
Elastin and Collagen Accumulation in Rabbit Ascending Aorta and Pulmonary Trunk During Postnatal Growth. Correlation of Cellular Synthetic Response With Medial Tension
,”
Circ. Res.
,
41
(
3
), pp.
316
323
.10.1161/01.RES.41.3.316
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