Interactions between structural remodeling and volumetric growth in right ventricle in response to pulmonary arterial hypertension.
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Pulmonary arterial hypertension (PAH) exerts substantial pressure overload on the right ventricle (RV). The associated RV free wall (RVFW) adaptation could consist of myocardial hypertrophy, augmented intrinsic contractility, collagen fibrosis, and structural remodeling in an attempt to cope with pressure overload. If RVFW adaptation cannot maintain the RV stroke volume, RV dilation will prevail as an exit mechanism which usually decompensates the RV function leading to RV failure. Our knowledge of the factors determining the transition from the upper limit of RVFW adaptation to RV decompensation and the role of fiber remodeling events in this transition remains very limited. Computational heart models that connect the growth and remodeling (G&R) events at the fiber and tissue levels with alterations in the organ-level function are essential to predict the temporal order and the compensatory level of the underlying mechanisms. In this work, building upon our recent rodent heart models (RHM) of PAH, we integrated mathematical models that describe time-evolution volumetric growth of the RV and structural remodeling of the RVFW. Results suggest that augmentation of the intrinsic contractility of myofibers accompanied by an increase in passive stiffness of RVFW is among the first remodeling events through which the RV strives to maintain the cardiac output. Interestingly, we found that the observed reorientation of the myofibers towards the longitudinal (apex-to-base) direction was a maladaptive mechanism that impaired the contractile pattern of RVFW and advanced along with RV dilation at later stages of PAH development.
author list (cited authors)
Avazmohammadi, R., Mendiola, E., Li, D., Vanderslice, P., Dixon, R., & Sacks, M.
complete list of authors
Avazmohammadi, Reza||Mendiola, Emilio||Li, David||Vanderslice, Peter||Dixon, Richard||Sacks, Michael