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A Computational Cardiac Model for the Adaptation to Pulmonary Arterial Hypertension in the Rat

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Abstract

Pulmonary arterial hypertension (PAH) imposes pressure overload on the right ventricle (RV), leading to RV enlargement via the growth of cardiac myocytes and remodeling of the collagen fiber architecture. The effects of these alterations on the functional behavior of the right ventricular free wall (RVFW) and organ-level cardiac function remain largely unexplored. Computational heart models in the rat (RHMs) of the normal and hypertensive states can be quite valuable in simulating the effects of PAH on cardiac function to gain insights into the pathophysiology of underlying myocardium remodeling. We thus developed high-fidelity biventricular finite element RHMs for the normal and post-PAH hypertensive states using extensive experimental data collected from rat hearts. We then applied the RHM to investigate the transmural nature of RVFW remodeling and its connection to wall stress elevation under PAH. We found a strong correlation between the longitudinally-dominated fiber-level adaptation of the RVFW and the transmural alterations of relevant wall stress components. We further conducted several numerical experiments to gain new insights on how the RV responds both normally and in the post-PAH state. We found that the effect of pressure overload alone on the increased contractility of the RV is comparable to the effects of changes in the RV geometry and stiffness. Furthermore, our RHMs provided fresh perspectives on long-standing questions of the functional role of the interventricular septum in RV function. Specifically, we demonstrated that an inaccurate identification of the mechanical adaptation of the septum can lead to a significant underestimation of RVFW contractility in the post-PAH state. These findings show how integrated experimental–computational models can facilitate a more comprehensive understanding of the cardiac remodeling events during PAH.

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Acknowledgments

We would like to thank Mr. Huan Nguyen at the University of Texas at Austin for assisting with part of simulations, and Dr. Lei Zhou at Texas Heart Institute for performing echocardiography of the rat hearts.

Funding

This work was supported by the US National Institutes of Health and American Heart Association awards (Nos. 5F32 HL132543-02 and 18CDA34110383, respectively) to R.A., the U.S. National Institutive of Healthy (Nos. T32EB007507 and F31HL139113) to D.S.L., and the W.A. Moncrief, Jr. SBES endowment to M.S.S.

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Authors and Affiliations

  1. Willerson Center for Cardiovascular Modeling and Simulation, Institute for Computational Engineering and Sciences and the Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA

    Reza Avazmohammadi, Emilio A. Mendiola, David S. Li & Michael S. Sacks

  2. Department of Mechanical & Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, USA

    João S. Soares

  3. Department of Molecular Cardiology, Texas Heart Institute, Houston, TX, USA

    Zhiqiang Chen, Peter Vanderslice & Richard A. F. Dixon

  4. Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA

    Samer Merchant & Edward W. Hsu

Authors
  1. Reza Avazmohammadi
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  2. Emilio A. Mendiola
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  3. João S. Soares
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  4. David S. Li
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  5. Zhiqiang Chen
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  7. Edward W. Hsu
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  8. Peter Vanderslice
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  9. Richard A. F. Dixon
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  10. Michael S. Sacks
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Correspondence to Michael S. Sacks.

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Associate Editor Ender A. Finol oversaw the review of this article.

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Avazmohammadi, R., Mendiola, E.A., Soares, J.S. et al. A Computational Cardiac Model for the Adaptation to Pulmonary Arterial Hypertension in the Rat. Ann Biomed Eng 47, 138–153 (2019). https://doi.org/10.1007/s10439-018-02130-y

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