A novel constitutive model for passive right ventricular myocardium: evidence for myofiber–collagen fiber mechanical coupling

Abstract

The function of right ventricle (RV) is recognized to play a key role in the development of many cardiopulmonary disorders, such as pulmonary arterial hypertension (PAH). Given the strong link between tissue structure and mechanical behavior, there remains a need for a myocardial constitutive model that accurately accounts for right ventricular myocardium architecture. Moreover, most available myocardial constitutive models approach myocardium at the length scale of mean fiber orientation, and do not explicitly account for different fibrous constituents and possible interactions among them. In the present work, we developed a fiber-level constitutive model for the passive mechanical behavior of the right ventricular free wall (RVFW) that explicitly distinguished between the mechanical contributions of myofiber and collagen fiber ensembles, and accounted for the fiber mechanical interactions. To obtain model parameters for the healthy passive RVFW, the model was informed by transmural orientation distribution measurements of myo- and collagen fibers, and was fit to the mechanical testing data, where both sets of data were obtained from recent experimental studies on non-contractile, but viable, murine RVFW specimens. Results supported the hypothesis that in the low strain regime the behavior of the RVFW is governed by myofiber response alone, which does not demonstrate any coupling between different myofiber ensembles. At higher strains, the collagen fibers and their interactions with myofibers begin to gradually contribute and dominate the behavior as recruitment proceeds. Due to the use of viable myocardial tissue, the contribution of myofibers was significant at all strains with the predicted tensile modulus of ~ 35 kPa. This was in contrast to earlier reports (Horowitz et al. 1988) where the contribution of myofibers was found to be insignificant. Also, we found that the interaction between myo- and collagen fibers was greatest under equibiaxial strain, with its contribution to the total stress not exceeding 20%. The present model can be applied to organlevel computational models of right ventricular dysfunction for efficient diagnosis and evaluation of pulmonary hypertension disorder.

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

“…5 and 6 and compare the low-strain regime responses; note that the longitudinal direction is nearly aligned with the mean myofiber direction.) Comparisons of the measured volume fraction and estimated values of myofiber stiffness (Table I) with corresponding values for normal tissues 20 further indicated that the myofiber stiffening stems primarily from an increase in the stiffness of myofibers (increased by ~75%), and secondarily from an increase in volume fraction of these fibers (increased by ~16%). In this connection, we recall from our experimental study 14 that the myofiber mass increased more than its volume leading to an ~40% increase to myofiber density.…”

“…This fraction was estimated to be about 3% for both normal and PAH cases ( ϕ g = 0.03). Next, following the recent approach, 20 we used 3-D Beta distribution functions Γ m ( θ m , z ) and Γ c ( θ c , z ) to present transmural distribution of myo- and collagen fibers orientation, respectively. Here, z denotes the normalized thickness varying between 0 at endocardium to 100 at epicardium along the transmural direction (denoted by x 3 ), and θ m , θ c ∈ [− π /2, π /2] are used to denote the planar orientation of myo- and collagen fibers, respectively (Fig.…”

“…Here, we summarize the main considerations and assumptions underlying our model, 20 The fibrous phases, consisting of myofibers and undulated collagen fibers, are considered to be the mechanically dominant. The mechanical contribution of the non-fibrous ground substance with a small volume fraction ϕ g was presented with a neo-Hookean term with a low stiffness k g .…”

“…This observation suggested that, for the post-PAH tissues, the contribution of collagen fibers to the overall stress and, in turn, the amount of fiber-fiber interactions could have a significant transmural variation which needs to be addressed within our modeling framework. For this reason, we extended our model, previously developed for the normal RVFW, 20 to include transmural variation in the volume fraction, collagen fiber recruitment properties, and the fiber-fiber interaction strength. The detail of this extension is described in this section.…”

“…Our objective in the present work was to utilize our novel myocardium constitutive modelling framework 20 to investigate RV remodeling on the passive behavior of the hypertension-induced, non-contracting, viable RVFW myocardium. 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.…”