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Research Papers

Obstruction-Induced Pulmonary Vascular Remodeling

[+] Author and Article Information
Ming-Jay Chow

Department of Mechanical Engineering,  Boston University, Boston, MA 02215jchow@bu.edu

Yu Zou

Department of Mechanical Engineering,  Boston University, Boston, MA 02215zou@bu.edu

Huamei He

Deparment of Anesthesia and Perioperative Medicine,  MUSC Storm Eye Institute, Charleston, SC 29403hehhu@musc.edu

Francis X. McGowan

Deparment of Anesthesia and Perioperative Medicine,  MUSC Storm Eye Institute, Charleston, SC 29403mcgowanf@musc.edu

David Zurakowski

Department of Anesthesiology,  Perioperative and Pain Medicine, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115david.zurakowski@childrens.harvard.edu

Yanhang Zhang1

Departments of Mechanical Engineering and Biomedical Engineering,  Boston University, 110 Cummington Street, Boston, MA 02215yanhang@bu.edu

1

Corresponding author.

J Biomech Eng 133(11), 111009 (Dec 08, 2011) (10 pages) doi:10.1115/1.4005301 History: Received June 13, 2011; Revised September 29, 2011; Posted October 14, 2011; Published December 08, 2011; Online December 08, 2011

Pulmonary obstruction occurs in many common forms of congenital heart disease. In this study, pulmonary artery (PA) banding is used as a model for pulmonary stenosis. Significant remodeling of the vascular bed occurs as a result of a prolonged narrowing of the PAs, and here we quantify the biophysical and molecular changes proximal and distal to the obstruction. Main and branch PAs are harvested from banded and sham rabbits and their mechanical properties are assessed using a biaxial tensile tester. Measurements defined as initial and stiff slopes are taken, assuming a linear region at the start and end of the J-shaped stress-strain curves, along with a transitional knee point. Collagen, elastin assays, Movat’s pentachrome staining, and Doppler protocols are used to quantify biochemical, structural, and physiological differences. The banded main PAs have significantly greater initial slopes while banded branch PAs have lower initial slopes; however, this change in mechanical behavior cannot be explained by the assay results as the elastin content in both main and branch PAs is not significantly different. The stiff slopes of the banded main PAs are higher, which is attributed to the significantly greater amounts of insoluble collagen. Shifting of the knee points reveals a decreased toe region in the main PAs but an opposite trend in the branch PAs. The histology results show a loss of integrity of the media, increase in ground substance, and dispersion of collagen in the banded tissue samples. This indicates other structural changes could have led to the mechanical differences in banded and normal tissue.

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Copyright © 2011 by American Society of Mechanical Engineers
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Figures

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Figure 1

Pictures of sham (a) and banded (b) PAs (outlined) during perfusion of the heart. Cleaned PAs from a sham (c) and banded (d) rabbit showing an increase in thickness and size of banded PAs. Arrows point to the banding sites in the banded PAs ((b) and (d)).

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Figure 2

Tricuspid regurgitation jet images showing longer decay time for banded (bottom) compared to sham (top) animals

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Figure 3

Average thickness of sham and banded PAs. *p < 0.05.

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Figure 4

Histological images of sham and banded main PAs using Movat’s Pentachrome stain (cut along circumference of artery). Collagen fibers (yellow), smooth muscle cells/fibrin (red), ground substance (blue), and nuclei/elastic fibers (black). Scale bar is 200 um.

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Figure 5

Histological images of sham and banded branch PAs using Movat’s Pentachrome stain (cut along circumference of artery). Collagen fibers (yellow), smooth muscle cells (red), ground substance (blue), and nuclei/elastic fibers (black). Scale bar is 200 um.

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Figure 6

(a) Example stress-strain curves showing the regions used to determine the initial and stiff slope along with the knee points. (b) Representative curves from the sham and banded main PAs. (c) Representative curves from the sham and banded branch PAs.

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Figure 7

Changes in initial slopes (a) and stiff slopes (b) in main and branch PAs. *p < 0.05.

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Figure 8

(a) Knee points for sham and banded main and branch PAs showing the general shift that occurred. (b) Quantitative comparisons of the knee point stresses and strains along with F values corresponding to the comparisons indicated by the brackets. *p < 0.05.

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Figure 9

Results of collagen assay showing the amounts of salt soluble, pepsin soluble, and insoluble collagen in the main (left) and branch (right) PAs. All values are reported as ug of collagen per mg of wet tissue weight. *p < 0.05.

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Figure 10

Correlation plots (a) between stiff slope and total collagen and (b) between stiff slope and cross-linked collagen of main PA. Total collagen is reported as ug of collagen per mg of wet tissue weight.

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