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Research Papers

Biaxial Properties of the Left and Right Pulmonary Arteries in a Monocrotaline Rat Animal Model of Pulmonary Arterial Hypertension

[+] Author and Article Information
Erica R. Pursell, Daniela Vélez-Rendón

Department of Bioengineering,
University of Illinois at Chicago,
Chicago, IL 60607

Daniela Valdez-Jasso

Assistant Professor
Department of Bioengineering,
University of Illinois at Chicago,
851 S Morgan Street, SEO 208,
Chicago, IL 60607
e-mail: dvj@uic.edu

1Corresponding author.

Manuscript received May 16, 2016; final manuscript received September 27, 2016; published online October 21, 2016. Assoc. Editor: Jessica E. Wagenseil.

J Biomech Eng 138(11), 111004 (Oct 21, 2016) (11 pages) Paper No: BIO-16-1203; doi: 10.1115/1.4034826 History: Received May 16, 2016; Revised September 27, 2016

In a monocrotaline (MCT) induced-pulmonary arterial hypertension (PAH) rat animal model, the dynamic stress–strain relation was investigated in the circumferential and axial directions using a linear elastic response model within the quasi-linear viscoelasticity theory framework. Right and left pulmonary arterial segments (RPA and LPA) were mechanically tested in a tubular biaxial device at the early stage (1 week post-MCT treatment) and at the advanced stage of the disease (4 weeks post-MCT treatment). The vessels were tested circumferentially at the in vivo axial length with matching in vivo measured pressure ranges. Subsequently, the vessels were tested axially at the mean pulmonary arterial pressure by stretching them from in vivo plus 5% of their length. Parameter estimation showed that the LPA and RPA remodel at different rates: axially, both vessels decreased in Young's modulus at the early stage of the disease, and increased at the advanced disease stage. Circumferentially, the Young's modulus increased in advanced PAH, but it was only significant in the RPA. The damping properties also changed in PAH; in the LPA relaxation times decreased continuously as the disease progressed, while in the RPA they initially increased and then decreased. Our modeling efforts were corroborated by the restructuring organization of the fibers imaged under multiphoton microscopy, where the collagen fibers become strongly aligned to the 45 deg angle in the RPA from an uncrimped and randomly organized state. Additionally, collagen content increased almost 10% in the RPA from the placebo to advanced PAH.

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Figures

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Fig. 1

(a) Isolated pulmonary arterial tree containing the main pulmonary artery (MPA), right pulmonary artery (RPA), and left pulmonary artery (LPA) of a rat. (b) Schematic of the segments harvested, where R2 and L1 are the segments used for mechanical testing, and R1 and L2 are used for multiphoton microscopy.

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Fig. 2

Summary of left ventricle + septum (LV + S) weight, Fulton index, mean pulmonary arterial pressure (mPAP), and right-ventricular systolic pressure (RVSP) for the placebo, MCT week 1, and MCT week 4 groups. *P < 0.05.

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Fig. 3

Representative maximum-intensity projections of multiphoton images taken through the vessel thickness of a (a) placebo LPA, (b) MCT week 1 LPA, (c) MCT week 4 LPA, (d) placebo RPA, (e) MCT week 1 RPA, and (f) MCT week 4 RPA. The collagen fibers organization changes from the normotensive to hypertensive states. Specifically, as the disease progresses, the fibers become less crimped, more dense, and more aligned halfway between the axial and circumferential directions. However, there is no noticeable change in the LPA. All the images have the same scale and are taken approximately at the same thickness depth.

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Fig. 4

Representative multiphoton images with arrows used for orientation analysis. Percent histograms of fiber orientations ranging from −90 deg to 90 deg on top left corners for (a) placebo LPA, (b) MCT week 1 LPA, (c) MCT week 4 LPA, (d) placebo RPA, (e) MCT week 1 RPA, and (f) MCT week 4 RPA. No apparent changes in the LPA, though fiber orientation becomes skewed toward 45 deg in the diseased RPA. All the images have the same scale and are taken approximately at the same thickness depth.

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Fig. 5

Cross-sectional histology slices of the right pulmonary arteries of a (a) placebo and (b) MCT week 4 animal. Collagen (blue) becomes more dense in the diseased state.

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Fig. 6

Representative circumferential pressure–area relation of the LPA (top row) and RPA (bottom row). On the left column—the placebo animal, middle column—the MCT-treated animal in the early stage of the disease (week 1), and on the right column, a MCT-treated animal in the acute stage of PAH (week 4). Experimental data are shown in light gray, and the model predictions are depicted in dark gray.

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Fig. 7

Representative axial length–force relation of the LPA (top row) and RPA (bottom row). On the left column—the placebo animal, middle column—the MCT—treated animal in the early stage of the disease (week 1), and on the right column—a MCT-treated animal in the acute stage of PAH (week 4). Experimental data are shown in light gray, and model predictions are depicted in dark gray.

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Fig. 8

Illustration of the interaction between treatment and artery type for the Young's modulus in the circumferential direction Eθ, and the natural log transformation of b1. Here the RPA of MCT week 4 was statistically significantly different (larger) than all the other vessels (disease stages and arteries) at a level of 0.05. The relaxation time in the circumferential direction b1.θ of the RPA at MCT week 1 was statistically significantly larger than the RPA of placebo and the LPA of MCT week 4.

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Fig. 9

Least squares means plots for the parameters with statistical significance in treatment effect. (a) A0 statistically significantly increases with the progression of PAH. In the axial direction, both Young's modulus Ez (b) and time relaxation b1,z. (c) showed the same adaptive changes: statistical changes at MCTW1 and no statistical difference between PL and MCT week 4. Statistical difference in relaxation time b1,z between LPA and RPA. *P < 0.05.

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