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

• Published in: Annals of biomedical engineering 2019-01, Vol.47 (1), p.138-153
• Main Authors: Avazmohammadi, Reza, Mendiola, Emilio A., Soares, João S., Li, David S., Chen, Zhiqiang, Merchant, Samer, Hsu, Edward W., Vanderslice, Peter, Dixon, Richard A. F., Sacks, Michael S.
• Format: Article
• Language: English
• Subjects: Adaptation; Animal models; Animals; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Biophysics; Blood pressure; Cardiac function; Cardiomyocytes; Classical Mechanics; Collagen; Computation; Computer applications; Computer Simulation; Disease Models, Animal; Enlargement; Finite element method; Heart; Hypertension; Hypertension, Pulmonary - pathology; Hypertension, Pulmonary - physiopathology; Male; Mathematical models; Models, Cardiovascular; Muscle contraction; Myocardium; Myocytes; Pressure effects; Pulmonary hypertension; Rats; Rats, Inbred F344; Septum; Stiffness; Ventricle; Ventricular Function, Right; Ventricular Remodeling
• ISSN: 0090-6964; 1573-9686
• DOI: 10.1007/s10439-018-02130-y

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.