TY - JOUR
T1 - Interactions between structural remodeling and hypertrophy in the right ventricle in response to pulmonary arterial hypertension
AU - Avazmohammadi, Reza
AU - Mendiola, Emilio A.
AU - Li, David S.
AU - Vanderslice, Peter
AU - Dixon, Richard A.F.
AU - Sacks, Michael S.
N1 - Funding Information:
This work was supported by the U.S. National Institutes of Health awards (Nos. K99 HL138288-01A1 and 5F32 HL132543-03) and an American Heart Association award (18CDA34110383) to RA and the W.A. Moncrief, Jr. SBES endowment to MSS. The authors were honored to contribute to the special issue for the 100th birthday of Dr. Y.C. Fung. In particular, MSS would like to acknowledge Dr. Fung for having a major influence in his career, both directly and indirectly. The following passage is written by MSS to recognize this influence.
Publisher Copyright:
Copyright © 2019 by ASME.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2019/9
Y1 - 2019/9
N2 - Pulmonary arterial hypertension (PAH) exerts substantial pressure overload on the right ventricle (RV), inducing RV remodeling and myocardial tissue adaptation often leading to right heart failure. The associated RV free wall (RVFW) adaptation involves 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 (SV), RV dilation will prevail as an exit mechanism, which usually decompensates 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 such as extracellular fibrosis and fiber reorientation 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 recently developed rodent heart models (RHM) of PAH, we integrated mathematical models that describe volumetric growth of the RV and structural remodeling of the RVFW. The timeevolution of RV remodeling from control and post-PAH time points was simulated. The results suggest that the 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 toward the longitudinal (apex-to-base) direction was a maladaptive mechanism that impaired the RVFW contractile pattern and advanced along with RV dilation at later stages of PAH. In fact, although individual fibers were more contractile post-PAH, the disruption in the optimal transmural fiber architecture compromised the effective contractile function of the RVFW, contributing to the depressed ejection fraction (EF) of the RV. Our findings clearly demonstrate the critical need for developing multiscale approaches that can model and delineate relationships between pathological alterations in cardiac function and underlying remodeling events across fiber, cellular, and molecular levels
AB - Pulmonary arterial hypertension (PAH) exerts substantial pressure overload on the right ventricle (RV), inducing RV remodeling and myocardial tissue adaptation often leading to right heart failure. The associated RV free wall (RVFW) adaptation involves 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 (SV), RV dilation will prevail as an exit mechanism, which usually decompensates 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 such as extracellular fibrosis and fiber reorientation 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 recently developed rodent heart models (RHM) of PAH, we integrated mathematical models that describe volumetric growth of the RV and structural remodeling of the RVFW. The timeevolution of RV remodeling from control and post-PAH time points was simulated. The results suggest that the 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 toward the longitudinal (apex-to-base) direction was a maladaptive mechanism that impaired the RVFW contractile pattern and advanced along with RV dilation at later stages of PAH. In fact, although individual fibers were more contractile post-PAH, the disruption in the optimal transmural fiber architecture compromised the effective contractile function of the RVFW, contributing to the depressed ejection fraction (EF) of the RV. Our findings clearly demonstrate the critical need for developing multiscale approaches that can model and delineate relationships between pathological alterations in cardiac function and underlying remodeling events across fiber, cellular, and molecular levels
KW - Adaptive and maladaptive mechanisms
KW - Cardiac remodeling
KW - Hypertrophy
KW - Pulmonary arterial hypertension
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U2 - 10.1115/1.4044174
DO - 10.1115/1.4044174
M3 - Article
C2 - 31260516
AN - SCOPUS:85096548040
VL - 141
JO - Journal of Biomechanical Engineering
JF - Journal of Biomechanical Engineering
SN - 0148-0731
IS - 9
M1 - 091016
ER -