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bioRxiv · 10.1101/2024.08.18.608471

Dissecting contributions of pulmonary arterial remodeling to right ventricular afterload in pulmonary hypertension

Neelakantan, S.·Mendiola, E. A.·Vang, A.·Myers, K. J.·Zhang, P.·Choudhary, G.·Avazmohammadi, R.
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Abstract

Pulmonary hypertension (PH) is defined as an elevation in the right ventricle (RV) afterload, characterized by increased hemodynamic pressure in the main pulmonary artery (PA). Elevations in RV afterload increase RV wall stress, resulting in RV remodeling and potentially RV failure. From a biomechanical standpoint, the primary drivers for RV afterload elevations include increases in pulmonary vascular resistance (PVR) in the distal vasculature and decreases in vessel compliance in the proximal PA. However, the individual contributions of the various vascular remodeling events toward the progression of PA pressure elevations and altered vascular hemodynamics remain elusive. In this study, we used a subject-specific one-dimensional (1D) fluid-structure interaction (FSI) model to investigate the alteration of pulmonary hemodynamics in PH and to quantify the contributions of vascular stiffening and increased resistance towards increased main pulmonary artery (MPA) pressure. We used a combination of subject-specific hemodynamic measurements, ex-vivo mechanical testing of arterial tissue specimens, and ex-vivo X-ray micro-tomography imaging to develop the 1D-FSI model and dissect the contribution of PA remodeling events towards alterations in the MPA pressure waveform. Both the amplitude and pulsatility of the MPA pressure waveform were analyzed. Our results indicated that increased distal resistance has the greatest effect on the increase in maximum MPA pressure, while increased stiffness caused significant elevations in the characteristic impedance. The method presented in this study will serve as an essential step toward understanding the complex interplay between PA remodeling events that leads to the most severe adverse effect on RV dysfunction.

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Neelakantan, S., Mendiola, E. A., Vang, A., Myers, K. J., Zhang, P., Choudhary, G., Avazmohammadi, R.. 2024-08-19. Dissecting contributions of pulmonary arterial remodeling to right ventricular afterload in pulmonary hypertension. https://doi.org/10.1101/2024.08.18.608471

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