0
Research Papers

Insights Into Regional Adaptations in the Growing Pulmonary Artery Using a Meso-Scale Structural Model: Effects of Ascending Aorta Impingement

[+] Author and Article Information
Bahar Fata

Department of Bioengineering,
University of Pittsburgh,
Pittsburgh, PA 19104;
Center for Cardiovascular Simulation,
Institute for Computational
Engineering and Science,
Department of Biomedical Engineering,
University of Texas,
Austin, TX 78712

Will Zhang

Center for Cardiovascular Simulation,
Institute for Computational
Engineering and Science,
Department of Biomedical Engineering,
University of Texas,
Austin, TX 78712

Rouzbeh Amini

Department of Biomedical Engineering,
Auburn Science and Engineering Center 275,
West Tower,
The University of Akron,
Akron, OH 44325

Michael S. Sacks

Professor
W. A. “Tex” Moncrief, Jr. Simulation-Based
Engineering Science Chair I,
Center for Cardiovascular Simulation,
Institute for Computational
Engineering and Science,
Department of Biomedical Engineering,
University of Texas,
Austin, TX 78712
e-mail: msacks@ices.utexas.edu

1Present address: Institute for Computational Engineering and Sciences (ICES), The University of Texas at Austin, 201 East 24th Street, ACES 5.438, 1 University Station, C0200, Austin TX 78712-0027.

2Corresponding author.

Contributed by the Bioengineering Division of ASME for publication in the Journal of Biomechanical Engineering. Manuscript received October 21, 2013; final manuscript received January 7, 2014; accepted manuscript posted January 10, 2014; published online February 5, 2014. Editor: Beth Winkelstein.

J Biomech Eng 136(2), 021009 (Feb 05, 2014) (13 pages) Paper No: BIO-13-1498; doi: 10.1115/1.4026457 History: Received October 21, 2013; Revised January 07, 2014; Accepted January 10, 2014

As the next step in our investigations into the structural adaptations of the main pulmonary artery (PA) during postnatal growth, we utilized the extensive experimental measurements of the growing ovine PA from our previous study (Fata et al., 2013, “Estimated in vivo Postnatal Surface Growth Patterns of the Ovine Main Pulmonary Artery and Ascending Aorta,” J. Biomech. Eng., 135(7), pp. 71010–71012). to develop a structural constitutive model for the PA wall tissue. Novel to the present approach was the treatment of the elastin network as a distributed fiber network rather than a continuum phase. We then utilized this model to delineate structure-function differences in the PA wall at the juvenile and adult stages. Overall, the predicted elastin moduli exhibited minor differences remained largely unchanged with age and region (in the range of 150 to 200 kPa). Similarly, the predicted collagen moduli ranged from ∼1,600 to 2700 kPa in the four regions studied in the juvenile state. Interestingly, we found for the medial region that the elastin and collagen fiber splay underwent opposite changes (collagen standard deviation juvenile = 17 deg to adult = 28 deg, elastin standard deviation juvenile = 35 deg to adult = 27 deg), along with a trend towards more rapid collagen fiber strain recruitment with age, along with a drop in collagen fiber moduli, which went from 2700 kPa for the juvenile stage to 746 kPa in the adult. These changes were likely due to the previously observed impingement of the relatively stiff ascending aorta on the growing PA medial region. Intuitively, the effects of the local impingement would be to lower the local wall stress, consistent with the observed parallel decrease in collagen modulus. These results suggest that during the postnatal somatic growth period local stresses can substantially modulate regional tissue microstructure and mechanical behaviors in the PA. We further underscore that our previous studies indicated an increase in effective PA wall stress with postnatal maturation. When taken together with the fact that the observed changes in mechanical behavior and structure in the growing PA wall were modest in the other three regions studied, our collective results suggest that the majority of the growing PA wall is subjected to increasing stress levels with age without undergoing major structural adaptations. This observation is contrary to the accepted theory of maintenance of homeostatic stress levels in the regulation of vascular function, and suggests alternative mechanisms might regulate postnatal somatic growth. Understanding the underlying mechanisms will help to improve our understanding of congenital defects of the PA and lay the basis for functional duplication in their repair and replacement.

FIGURES IN THIS ARTICLE
<>
Copyright © 2014 by ASME
Your Session has timed out. Please sign back in to continue.

References

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. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
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. [PubMed]
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. [PubMed]
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. [CrossRef] [PubMed]
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), pp. I159–I166. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
Wang, Z., and Chesler, N. C., 2011, “Pulmonary Vascular Wall Stiffness: An Important Contributor to the Increased Right Ventricular Afterload With Pulmonary Hypertension,” Pulmonary Circulation, 1(2), pp. 212–223. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
Langille, B. L., Brownlee, R. D., and Adamson, S. L., 1990, “Perinatal Aortic Growth in Lambs: Relation to Blood Flow Changes at Birth,” Am. J. Physiol., 259(28), pp. H1247–H1253. [PubMed]
Tucker, A., Migally, N., Wright, M. L., and Greenlees, K. J., 1984, “Pulmonary Vascular Changes in Young and Aging Rats Exposed to 5,486 M Altitude,” Respiration, 46(3), pp. 246–257. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
Mceniery, C. M., Wilkinson, I. B., and Avolio, A. P., 2007, “Age, Hypertension, and Arterial Function,” Clin. Exp. Pharmacol. Physiol., 34(7), pp. 665–671. [CrossRef] [PubMed]
Schwartz, C. J., Valente, A. J., Sprague, E. A., Kelley, J. L., and Nerem, R. M., 1991, “The Pathogenesis of Atherosclerosis: An Overview,” Clin. Cardiol., 14(2), pp. I1–16. [CrossRef] [PubMed]
Fata, B., Gottlieb, D., Mayer, J. E., and Sacks, M. S., 2013, “Estimated In Vivo Postnatal Surface Growth Patterns of the Ovine Main Pulmonary Artery and Ascending Aorta,” ASME J. Biomech. Eng., 135(7), p. 071010. [CrossRef]
Gottlieb, D., Fata, B., Powell, A. J., Cois, C. A., Annese, D., Tandon, K., Stetten, G., Mayer, J. E., Jr., and Sacks, M. S., 2013, “Pulmonary Artery Conduit In Vivo Dimensional Requirements in a Growing Ovine Model: Comparisons With the Ascending Aorta,” J. Heart Valve Dis., 22(2), pp. 195–203. [PubMed]
Fata, B., Carruthers, C. A., Gibson, G., Watkins, S. C., Gottlieb, D., Mayer, J. E., and Sacks, M. S., 2013, “Regional Structural and Biomechanical Alterations of the Ovine Main Pulmonary Artery During Postnatal Growth,” ASME J. Biomech. Eng., 135(2), p. 021022. [CrossRef]
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. [CrossRef] [PubMed]
Hollander, Y., Durban, D., Lu, X., Kassab, G. S., and Lanir, Y., 2011, “Constitutive Modeling of Coronary Arterial Media–Comparison of Three Model Classes,” ASME J. Biomech. Eng., 133(6), p. 061008. [CrossRef]
Hansen, L., Wan, W., and Gleason, R. L., 2009, “Microstructurally Motivated Constitutive Modeling of Mouse Arteries Cultured Under Altered Axial Stretch,” ASME J. Biomech. Eng., 131(10), p. 101015. [CrossRef]
Hunter, K. S., Lanning, C. J., Chen, S. Y., Zhang, Y., Garg, R., Ivy, D. D., and Shandas, R., 2006, “Simulations of Congenital Septal Defect Closure and Reactivity Testing in Patient-Specific Models of the Pediatric Pulmonary Vasculature: A 3D Numerical Study With Fluid-Structure Interaction,” ASME J. Biomech. Eng., 128(4), pp. 564–572. [CrossRef]
Zhang, Y., Dunn, M. L., Hunter, K. S., Lanning, C., Ivy, D. D., Claussen, L., Chen, S. J., and Shandas, R., 2007, “Application of a Microstructural Constitutive Model of the Pulmonary Artery to Patient-Specific Studies: Validation and Effect of Orthotropy,” ASME J. Biomech. Eng., 129(2), pp. 193–201. [CrossRef]
Kao, P. H., Lammers, S., Tian, L., Hunter, K., Stenmark, K. R., Shandas, R., and Qi, H. J., 2011, “A Microstructurally Driven Model for Pulmonary Artery Tissue,” ASME J. Biomech. Eng., 133(5), p. 051002. [CrossRef]
Zulliger, M. A., Rachev, A., and Stergiopulos, N., 2004, “A Constitutive Formulation of Arterial Mechanics Including Vascular Smooth Muscle Tone,” Am. J. Physiol. Heart Circ. Physiol., 287(3), pp. H1335–H1343. [CrossRef] [PubMed]
Lanir, Y.1983, “Constitutive Equations for Fibrous Connective Tissues,” J. Biomech., 16, pp. 1–12. [CrossRef] [PubMed]
Fung, Y. C., 1993, Biomechanics: Mechanical Properties of Living Tissues, Springer Verlag, New York.
Sacks, M. S., 2003, “Incorporation of Experimentally-Derived Fiber Orientation Into a Structural Constitutive Model for Planar Collagenous Tissues,” ASME J. Biomech. Eng., 125(2), pp. 280–287. [CrossRef]
Smith, D. B., Sacks, M. S., Vorp, D. A., and Thornton, M., 2000, “Surface Geometric Analysis of Anatomic Structures Using Biquintic Finite Element Interpolation,” Ann. Biomed. Eng., 28(6), pp. 598–611. [CrossRef] [PubMed]
Sacks, M. S., 2000, “A Structural Constitutive Model for Chemically Treated Planar Connective Tissues Under Biaxial Loading,” Comput. Mech., 26(3), pp. 243–249. [CrossRef]
Humphrey, J. D., 2009, “Vascular Mechanics, Mechanobiology, and Remodeling,” J. Mech. Med. Biol., 9(2), pp. 243–257. [CrossRef] [PubMed]
Ambrosi, D., Ateshian, G. A., Arruda, E. M., Cowin, S. C., Dumais, J., Goriely, A., Holzapfel, G. A., Humphrey, J. D., Kemkemer, R., Kuhl, E., Olberding, J. E., Taber, L. A., and Garikipati, K., 2011, “Perspectives on Biological Growth and Remodeling,” J. Mech. Phys. Solids, 59(4), pp. 863–883. [CrossRef] [PubMed]
Gasser, T. C., Ogden, R. W., and Holzapfel, G. A., 2006, “Hyperelastic Modelling of Arterial Layers With Distributed Collagen Fibre Orientations,” J. R. Soc., Interface, 3(6), pp. 15–35. [CrossRef]
Zulliger, M. A., Fridez, P., Hayashi, K., and Stergiopulos, N., 2004, “A Strain Energy Function for Arteries Accounting for Wall Composition and Structure,” J. Biomech., 37(7), pp. 989–1000. [CrossRef] [PubMed]
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. [CrossRef] [PubMed]
Sherebrin, M. H., Song, S. H., and Roach, M. R., 1983, “Mechanical Anisotropy of Purified Elastin from the Thoracic Aorta of Dog and Sheep,” Can. J. Physiol. Pharmacol., 61, pp. 539–545. [CrossRef] [PubMed]
Ogden, R. W., and Saccomandi, G., 2007, “Introducing Mesoscopic Information Into Constitutive Equations for Arterial Walls,” Biomech. Modeling Mechanobiol., 6(5), pp. 333–344. [CrossRef]
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. [CrossRef] [PubMed]
Bischoff, J. E., Arruda, E. M., and Grosh, K., 2002, “A Microstructurally Based Orthotropic Hyperelastic Constitutive Law,” ASME J. Appl. Mech., 69(5), pp. 570–579. [CrossRef]
Mithieux, S. M., and Weiss, A. S., 2005, “Elastin,” Adv. Protein Chem., 70, pp. 437–461. [CrossRef] [PubMed]
Roccabianca, S., Ateshian, G. A., and Humphrey, J. D., 2013, “Biomechanical Roles of Medial Pooling of Glycosaminoglycans in Thoracic Aortic Dissection,” Biomech. Model Mechanobiol., 13(1), pp. 13–25. [CrossRef]
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 Measured Collagen Orientation and Recruitment into Mechanical Models of the Artery Wall,” J. Biomech., 45(5), pp. 762–771. [CrossRef] [PubMed]

Figures

Grahic Jump Location
Fig. 1

(a) 3D reconstruction of the ovine ascending aorta (AA) and the pulmonary artery showing the pulmonary trunk (PT) view, with the white dashed box indicating area of contact between the two great vessels. Also shown are the posterior, anterior, lateral, and medial regions of the PA. (b) Transmural micrograph of the ovine PA and volume fraction results of the PA at the juvenile and adult states. Note that all regions demonstrated an increase in collagen mass with age, with the medial region indicating the largest mass fraction in the adult state.

Grahic Jump Location
Fig. 2

Final average elastin and collagen measured orientation distributions and the Modified Beta distribution probability distribution fits in the juvenile and adult states

Grahic Jump Location
Fig. 3

(a) Results of the bicubic Hermite surface interpolation of the 2nd Piola-Kirchhof stress biaxial test responses to allow interpolation of an equi-biaxial strain path, shown here in red. (b) Fit of the medial region collagen fiber recruitment using a Beta cumulative distribution function for both juvenile and adult states, revealing both an excellent fit to the data along with a trend towards more rapid recruitment with strain in the adult stage.

Grahic Jump Location
Fig. 4

Fiber ensemble stress-strain results for the interpolated equi-biaxial strain path responses for all four regions at both age time points

Grahic Jump Location
Fig. 5

Fiber ensemble tangent modulus-strain results for the interpolated equi-biaxial strain path responses for all four regions at both age time points. Note here the sharp increase in stiffness due to collagen fiber engagement (arrows). Also note the decreases in stiffness with age in the lateral and medial regions.

Grahic Jump Location
Fig. 6

Using the results of Fig. 5, the collagen engagement strain (Elb) results for all four regions at both age time points. There were in general slightly large values for the anterior and lateral regions, and minimal changes with age.

Grahic Jump Location
Fig. 7

(a) Constitutive model fit to the average five-protocol biaxial stress-stretch data (protocols 2–6, see inset) of juvenile and adult medial PA wall specimens. (b) Predicted fit results to protocols 1 and 7 (see inset), showing excellent agreement.

Grahic Jump Location
Fig. 8

Predicted collagen and elastin moduli for the medial region using the actual experimental data and the β distributions. No differences were observed, suggesting the modified Beta distribution for the fiber splay (see Fig. 2) is sufficient to capture the in-plane responses of the ovine PA.

Grahic Jump Location
Fig. 9

Predicted values for (a) elastin (de) and (b) collagen (dc) values for all four regions at both age time points. Here the medial region had the large values for de (statistically different from the anterior and posterior regions), whereas dc exhibited no statistically significant regional or age differences.

Grahic Jump Location
Fig. 10

Predicted fiber splay deviation parameter σ for (a) elastin (σe) and (b) collagen (σc) fibers for all four regions at both age time points. While some modest differences with region and age occurred, the main finding was the medial region's drop in σe and increase in σc with age. Values presented as radians, and in degrees these changes are σc: juvenile = 17 deg to adult = 28 deg, σe: juvenile = 35 deg to adult = 27 deg.

Grahic Jump Location
Fig. 11

Predicted collagen fiber recruitment for (a) mean (μr) and (b) standard deviation (σr) for all four regions at both age time points. The main observed changes were found for σr, which demonstrated decreases with age in the anterior, posterior, and lateral regions, but an increase in the medial region.

Grahic Jump Location
Fig. 12

Predicted (a) collagen (κc) and (b) elastin (κe) fiber moduli regions at both age time points. The most drastic changes were for the elastin modulus ke increasing by ∼50% and the collagen modulus kc decreasing to only ∼25% of the juvenile value in the medial region.

Tables

Errata

Discussions

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In