Structural and Mechanical Adaptations of Right Ventricle Free Wall Myocardium to Pressure Overload

Abstract

Right ventricular (RV) failure in response to pulmonary hypertension (PH) is a severe disease that remains poorly understood. PH-induced pressure overload leads to changes in the RV free wall (RVFW) that eventually results in RV failure. While the development of computational models can benefit our understanding of the onset and progression of PH-induced pressure overload, detailed knowledge of the underlying structural and biomechanical events remains limited. The goal of the present study was to elucidate the structural and biomechanical adaptations of RV myocardium subjected to sustained pressure overload in a rat model. Hemodynamically confirmed severe chronic RV pressure overload was induced in Sprague-Dawley rats via pulmonary artery banding. Extensive tissue-level biaxial mechanical and histomorphological analyses were conducted to assess the remodeling response in the RV free wall. Simultaneous myofiber hypertrophy and longitudinal re-orientation of myo- and collagen fibers was observed, with both fiber types becoming more highly aligned. Transmural myo- and collagen fiber orientations were co-aligned in both the normal and diseased state. The overall tissue stiffness increased, with larger increases in longitudinal versus circumferential stiffness. Interestingly, estimated myofiber stiffness increased while the collagen fiber stiffness remained unchanged. The latter was attributed to longitudinal fiber re-orientation, which increased the degree of anisotropy. Increased mechanical coupling between the two axes was attributed to the increased fiber alignment. The increased myofiber stiffness was consistent with clinical results showing titin-associated increased sarcomeric stiffening observed in PH patients. These results further our understanding of the underlying adaptive and maladaptive remodeling mechanisms and may lead to improved techniques for prognosis, diagnosis, and treatment for PH.

Biomechanical Properties and Microstructure of Heart Chambers: A Paired Comparison Study in an Ovine Model

“…The results showed a significant increase in stiffness leading up to 2 weeks and then showed a significant decrease in stiffness at 6 weeks. In another study, Hill et al 9 studied the structural and mechanical adaptations of right ventricle free wall myocardium due to pulmonary hypertension in a rat model. Biaxial mechanical studies were performed on isolated myocardium obtained from normotensive and hypertensive hearts.…”

Biomechanical properties and microstructure of human ventricular myocardium

“…In the literature, the passive biaxial extension properties of the myocardium were documented [23][24][25][26][27][28], which mainly come from equibiaxial extension tests on hearts from mongrel dogs; only Yin et al [24] performed 'true' biaxial extension tests with different ratios (as distinct from equibiaxial tests) on mongrel dogs, a study performed more than 25 years ago. The biaxial data of dog hearts indicate highly nonlinear and anisotropic properties.…”

Transmural remodeling of right ventricular myocardium in response to pulmonary arterial hypertension

“…The right ventricular free wall (RVFW) consists of myofibers (also known as cardiomyocytes or muscle cells), collagen fibers, a vascular network, and an amorphous ground matrix. 14 The underlying mechanisms of G&R responses at the fiber level to the increased ventricular pressure can be of two main types. The first type, associated with growth (hypertrophy), induces changes in mass and volume of myo- and collagen fiber aggregates [Fig.…”

“…In particular, recent studies 14,16 on the mechanical and morphological properties of normal and hypertensive RVFW myocardium strongly suggest that myocardial wall stress is the primary mediator of RVFW growth and remodeling responses. This is consistent with the traditional view that G&R responses are triggered by a disturbance in the homeostatic equilibrium of local stresses.…”

“…To estimate the parameters of the model, we used the extensive mechanical and transmural histological data from recent murine experimental studies for both control (normal) and post (3-week) hypertensive states. 14,16 In contrast to prior works 14,16 that provided insights into the “global” remodeling mechanisms during PAH, the current study aimed to quantify and analyze changes in the contribution of each fiber type at the tissue level and the transmural “locality” of these changes, using the implementation of the fiber-specific structural model. Moreover, using a Laplace model, we investigated the correlation between fiber-level adaptations and the changes in the wall stress components at the organ level.…”