No 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.

BackgroundRight ventricular (RV) diastolic function has been associated with outcomes for patients with pulmonary hypertension; however, the relationship between biomechanics and hemodynamics in the right ventricle has not been studied.Methods and ResultsRat models of RV pressure overload were obtained via pulmonary artery banding (PAB; control, n=7; PAB, n=5). At 3 weeks after banding, RV hemodynamics were measured using a conductance catheter. Biaxial mechanical properties of the RV free wall myocardium were obtained to extrapolate longitudinal and circumferential elastic modulus in low and high strain regions (E1 and E2, respectively). Hemodynamic analysis revealed significantly increased end‐diastolic elastance (Eed) in PAB (control: 55.1 mm Hg/mL [interquartile range: 44.7–85.4 mm Hg/mL]; PAB: 146.6 mm Hg/mL [interquartile range: 105.8–155.0 mm Hg/mL]; P=0.010). Longitudinal E1 was increased in PAB (control: 7.2 kPa [interquartile range: 6.7–18.1 kPa]; PAB: 34.2 kPa [interquartile range: 18.1–44.6 kPa]; P=0.018), whereas there were no significant changes in longitudinal E2 or circumferential E1 and E2. Last, wall stress was calculated from hemodynamic data by modeling the right ventricle as a sphere: )(stress=Pressure×radius2×thickness.Conclusions RV pressure overload in PAB rats resulted in an increase in diastolic myocardial stiffness reflected both hemodynamically, by an increase in Eed, and biomechanically, by an increase in longitudinal E1. Modest increases in tissue biomechanical stiffness are associated with large increases in Eed. Hemodynamic measurements of RV diastolic function can be used to predict biomechanical changes in the myocardium.

We present a model for the rheological behaviour of non-dilute suspensions of initially spherical viscoelastic particles in viscous fluids under uniform Stokes flow conditions. The particles are assumed to be neutrally buoyant Kelvin-Voigt solids undergoing time-dependent finite deformations and exhibiting generalized neo-Hookean behaviour in their purely elastic limit. We investigate the effects of the shape dynamics and constitutive properties of the viscoelastic particles on the macroscopic rheological behaviour of the suspensions. The proposed model makes use of known homogenization estimates for composite material systems consisting of random distributions of aligned ellipsoidal particles with prescribed two-point correlation functions to generate corresponding estimates for the instantaneous (incremental) response of the suspensions, together with appropriate evolution laws for the relevant microstructural variables. To illustrate the essential features of the model, we consider two special cases: (i) extensional flow and (ii) simple shear flow. For each case, we provide the time-dependent response and, when available, the steady-state solution for the average particle shape and orientation, as well as for the effective viscosity and normal stress differences in the suspensions. The results exhibit shear thickening for extensional flows and shear thinning for simple shear flows, and it is found that the volume fraction and constitutive properties of the particles significantly influence the rheology of the suspensions under both types of flows. In particular, for extensional flows, suspensions of particles with finite extensibility constraints are always found to reach a steady state, while this is only the case at sufficiently low strain rates for suspensions of (less realistic) neo-Hookean particles, as originally reported by Roscoe (J.

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.