Research Papers

Right Ventricular Fiber Structure as a Compensatory Mechanism in Pressure Overload: A Computational Study

[+] Author and Article Information
Arnold D. Gomez

Electrical and Computer Engineering Department,
Johns Hopkins University,
3400 North Charles Street, RM Clark 201B,
Baltimore, MD 21218
e-mail: adgomez@jhu.edu

Huashan Zou

Bioengineering Department,
University of Utah,
36 S. Wasatch Drive, SMBB RM 3100,
Salt Lake City, UT 84112-2101
e-mail: u0725547@utah.edu

Megan E. Bowen

Surgery Department,
University of Utah,
30 N 1900 E, RM 3B205,
Salt Lake City, UT 84112-2101
e-mail: megan.bowen@hsc.utah.edu

Xiaoqing Liu

Cardiothoracic Division,
Surgery Department,
University of Utah,
2000 Circle of Hope, RM LL376,
Salt Lake City, UT 84112-2101
e-mail: annie.liu@hci.utah.edu

Edward W. Hsu

Bioengineering Department,
University of Utah,
36 S. Wasatch Drive, SMBB RM 1242,
Salt Lake City, UT 84112-2101
e-mail: edward.hsu@utah.edu

Stephen H. McKellar

Cardiothoracic Division,
Surgery Department,
University of Utah,
30 N 1900 E, RM 3B205
Salt Lake City, UT 84112-2101
e-mail: stephen.mckellar@hsc.utah.edu

Manuscript received November 7, 2016; final manuscript received April 7, 2017; published online June 7, 2017. Assoc. Editor: Hai-Chao Han.

J Biomech Eng 139(8), 081004 (Jun 07, 2017) (10 pages) Paper No: BIO-16-1444; doi: 10.1115/1.4036485 History: Received November 07, 2016; Revised April 07, 2017

Right ventricular failure (RVF) is a lethal condition in diverse pathologies. Pressure overload is the most common etiology of RVF, but our understanding of the tissue structure remodeling and other biomechanical factors involved in RVF is limited. Some remodeling patterns are interpreted as compensatory mechanisms including myocyte hypertrophy, extracellular fibrosis, and changes in fiber orientation. However, the specific implications of these changes, especially in relation to clinically observable measurements, are difficult to investigate experimentally. In this computational study, we hypothesized that, with other variables constant, fiber orientation alteration provides a quantifiable and distinct compensatory mechanism during RV pressure overload (RVPO). Numerical models were constructed using a rabbit model of chronic pressure overload RVF based on intraventricular pressure measurements, CINE magnetic resonance imaging (MRI), and diffusion tensor MRI (DT-MRI). Biventricular simulations were conducted under normotensive and hypertensive boundary conditions using variations in RV wall thickness, tissue stiffness, and fiber orientation to investigate their effect on RV pump function. Our results show that a longitudinally aligned myocardial fiber orientation contributed to an increase in RV ejection fraction (RVEF). This effect was more pronounced in response to pressure overload. Likewise, models with longitudinally aligned fiber orientation required a lesser contractility for maintaining a target RVEF against elevated pressures. In addition to increased wall thickness and material stiffness (diastolic compensation), systolic mechanisms in the forms of myocardial fiber realignment and changes in contractility are likely involved in the overall compensatory responses to pressure overload.

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Grahic Jump Location
Fig. 1

Numerical experiments. The sensitivity study encompassed two experiments aimed at determining differences between models with baseline and baseline fiber distribution. The first experiment (left) looked at differences in RV ejection fraction (RVEF). The second experiment (right) investigated differences in active contraction, or contractility given a target RVEF. Each of the modeling parameters included a nominal value based on normal RVs and a modification based on pressure overload.

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Fig. 2

Biventricular mesh. The complete mesh (top) was subdivided into four compartments: the RV free wall, the RV insertion, the LV (including the septum), and a low-stiffness support material. The potential distribution (bottom) was used as rule for fiber distribution, which provided a smooth transition from LV to RV for modeling differences in HAS.

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Fig. 3

Modeled fiber distribution. The tractographical representation of a baseline model (a) and a model with longitudinally aligned fibers (b) show differences in RV fiber orientation (circle). The baseline fibers are more circumferential and have less steep angles than the longitudinally aligned fiber distribution.

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Fig. 4

Helix angle measurements from basal DT-MRI slices and linear approximations. The RV (left) exhibits more nonlinearity than the (LV). The RV has a steeper distribution on the endocardial (ENDO) half, compared to its epicardial (EPI) counterpart. The nominal linear fiber distributions were the same in the LV and the RV, and modifications were only applied to the RV.

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Fig. 5

High-resolution imaging of the ventricles. Imaging from a representative control animal (left column) exhibits relatively thin RV wall compared to the LV (right column). These differences were captured by the meshes with (thick-walled RV) and without (normal) modifications in wall thickness.

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Fig. 6

Comparison between normal and RVPO simulations. Introducing pressure overload conditions (increased boundary pressures) results in marked diastolic ventricular deformation characterized by an enlarged RV and septal bowing, which give the LV a “D” shape. These differences are virtually unnoticeable during systole.

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Fig. 7

Per-animal (A1–A3) grouping of differences between baseline (B), and longitudinally aligned (L) fiber distribution. A small but consistent decrease in systolic volume was observed both in the normotensive (top) and the hypertensive (middle) groups. This change produced an increment in stroke volume, and, consequently, RVEF. The differences in RVEF (bottom) are more pronounced in the hypertensive group.

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Fig. 8

Simulation type grouping of differences between B and L fiber distribution. This grouping shows a similar trend to Fig. 7, with the L group resulting in lowered systolic volumes compared to B, in both the normotensive (top) and the hypertensive (middle) groups. Grouping the results by simulation type shows the effect of stiffness on diastolic volume. Compared to nominal models (N), models with a thicker wall (T) were more stiff and this translated to a reduction in diastolic volume. Increased material stiffness (S), and a combination of T and S (T&S) progressively exacerbated these reductions. As in the per-animal grouping, the differences in RVEF (bottom) were more pronounced in the hypertensive group.

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Fig. 9

Contractility differences for maintaining normal RVEF. Because models in pressure overload conditions (RVPO) change volume against higher pressures, contractility values are larger than in the normal simulations. However, modifying the models to include longitudinal alignment (L) results in a small, but consistent reduction in contractility compared to the baseline fiber orientation (B).



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