Abstract
Pulmonary arterial hypertension (PAH) imposes substantial pressure overload on the right ventricular free wall (RVFW), leading to myofiber hypertrophy and remodeling of its collagen fiber architecture. The transmural nature of these adaptations and their effects on the macroscopic mechanical behavior of the RVFW remain largely unexplored. In the present work, we extended our constitutive model for RVFW myocardium to investigate the transmural mechanical and structural remodeling post-PAH. Recent murine experimental studies provided us with comprehensive histomorphological and biaxial mechanical data for viable, passive myocardium for normal and post hypertensive cases. Multiple fiber-level remodeling events were found to be localized in the midwall region (40% < depth < 60%): (i) reorientation and alignment of both myo- and collagen fibers towards longitudinal (apex-to-outflow tract) direction, (ii) substantial increase in the rate of the recruitment of collagen fibers with strain, and (iii) a corresponding increase in the mechanical interactions between the collagen and myofibers. These adaptations suggest a denser and more fibrous connective tissue in the midwall region, and led to a substantially stiffer mechanical response along the longitudinal direction in post-PAH tissues. Moreover, using a Laplace-type mechanical equilibrium analysis of the right ventricle to approximate the wall stress state, we estimated that the longitudinal component of stress remained higher in the hypertensive state while the circumferential component approximately maintained homeostasis values. This result was consistent with our observation from the fiber- and tissue-level remodeling that longitudinally oriented collagen fibers, localized in the midwall region, dominated the remodeling process. The findings of this study highlight the need for more integrated cellular-tissue-organ analysis to better understand the remodeling events during PAH and design interventions.
Highlights
Right ventricular (RV) failure is a major cause of mortality for patients suffering from pulmonary arterial hypertension (PAH) with a mortality rate of 37.2% at 3 years post-diagnosis.1,2 The health and status of the right ventricle of the heart has been shown to be a key indicator of overall progression of Pulmonary arterial hypertension (PAH),3 and a good predictor of survival for patients suffering from this diseases
We extended our constitutive model for right ventricular free wall (RVFW) myocardium to investigate the transmural mechanical and structural remodeling post-PAH
The 3D Beta-distribution surfaces extracted from histological analysis of 3-week PAH tissues revealed that both myo- and collagen fibers exhibited a fairly uniform shift in the orientation towards the longitudinal direction with a more pronounced alignment of fibers in the midwall region, again towards the longitudinal direction (Fig. 3)
Summary
Right ventricular (RV) failure is a major cause of mortality for patients suffering from pulmonary arterial hypertension (PAH) with a mortality rate of 37.2% at 3 years post-diagnosis. The health and status of the right ventricle of the heart has been shown to be a key indicator of overall progression of PAH, and a good predictor of survival for patients suffering from this diseases. There have been many clinical studies assessing the hypertrophy and remodeling processes taking place during PAH, as well as in investigating whether or not these processes are reversible.. There have been many clinical studies assessing the hypertrophy and remodeling processes taking place during PAH, as well as in investigating whether or not these processes are reversible.9,10 The foundation of such studies must rest on an understanding of changes in the structure-function relationship that occur during RV hypertrophy and remodeling. Such an understanding is essential in developing computational biomechanical models of the RV. Relatively little known of the structural and mechanical alterations of the right ventricular free wall (RVFW) myocardium during PAH and its relation to parallel changes in RV function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
