Abstract Although detailed cell‐based descriptors of cross‐bridge cycling have been applied in finite element (FE) heart models to describe ventricular mechanics, these multiscale models have never been tested rigorously to determine if these descriptors, when scaled up to the organ‐level, are able to reproduce well‐established organ‐level physiological behaviors. To address this void, we here validate a left ventricular (LV) FE model that is driven by a cell‐based cross‐bridge cycling descriptor against key organ‐level heart physiology. The LV FE model was coupled to a closed‐loop lumped parameter circulatory model to simulate different ventricular loading conditions (preload and afterload) and contractilities. We show that our model is able to reproduce a linear end‐systolic pressure volume relationship, a curvilinear end‐diastolic pressure volume relationship and a linear relationship between myocardial oxygen consumption and pressure – volume area. We also show that the validated model can predict realistic LV strain‐time profiles in the longitudinal, circumferential, and radial directions. The predicted strain‐time profiles display key features that are consistent with those measured in humans, such as having similar peak strains, time‐to‐peak‐strain, and a rapid change in strain during atrial contraction at late‐diastole. Our model shows that the myocardial strains are sensitive to not only LV contractility, but also to the LV loading conditions, especially to a change in afterload. This result suggests that caution must be exercised when associating changes in myocardial strain with changes in LV contractility. The methodically validated multiscale model will be used in future studies to understand human heart diseases.
Recent clinical studies have reported that heart failure with preserved ejection fraction (HFpEF) can be divided into two phenotypes based on the range of ejection fraction (EF), namely HFpEF with higher EF and HFpEF with lower EF. These phenotypes exhibit distinct left ventricle (LV) remodelling patterns and dynamics. However, the influence of LV remodelling on various LV functional indices and the underlying mechanics for these two phenotypes are not well understood. To address these issues, this study employs a coupled finite element analysis (FEA) framework to analyse the impact of various ventricular remodelling patterns, specifically concentric remodelling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH), with and without LV wall thickening on LV functional indices. Further, the geometries with a moderate level of remodelling from each pattern are subjected to fibre stiffening and contractile impairment to examine their effect in replicating the different features of HFpEF. The results show that with severe CR, LV could exhibit the characteristics of HFpEF with higher EF, as observed in recent clinical studies. Controlled fibre stiffening can simultaneously increase the end-diastolic pressure (EDP) and reduce the peak longitudinal strain (e
Molecular dynamics simulations have been conducted to reveal the effect of solid-liquid interfacial wettability on the boiling phenomena of the thin liquid argon film placed over solid platinum wall. The three phase molecular system is comprised of solid platinum wall, liquid argon and argon vapor. Initially the three phase system is thermally equilibrated at 90 K and after the attainment of equilibrium the temperature of solid platinum wall is suddenly increased which resembles ultrafast pulse heating. Two different degree of superheat have been considered to characterize the boiling phenomena, namely, evaporation for low degree of superheat and rapid or explosive boiling for high degree of superheat in which temperature of the wall was far above the critical temperature of argon. The solid-liquid interfacial wettability is varied to observe its effect on boiling and thus simulations are run for hydrophilic, hydrophobic and neutral surfaces. The simulation results show that surface wettability has a significant role on both cases of boiling phenomena. The nucleation of bubbles and formation of vapor films occurs more quickly for increased solid-liquid interfacial wettability. The study shows that hydrophilic surface is the most favorable surface condition for bubble nucleation.
Molecular dynamics (MD) simulations have been carried out to investigate evaporation and explosive boiling phenomena of thin film liquid argon on nanostructured solid surface with emphasis on the effect of solid-liquid interfacial wettability. The nanostructured surface considered herein consists of trapezoidal internal recesses of the solid platinum wall. The wetting conditions of the solid surface were assumed such that it covers both the hydrophilic and hydrophobic conditions and hence effect of interfacial wettability on resulting evaporation and boiling phenomena was the main focus of this study. The initial configuration of the simulation domain comprised of a three phase system (solid platinum, liquid argon and vapor argon) on which equilibrium molecular dynamics (EMD) was performed to reach equilibrium state at 90 K. After equilibrium of the three-phase system was established, the wall was set to different temperatures (130 K and 250 K for the case of evaporation and explosive boiling respectively) to perform non-equilibrium molecular dynamics (NEMD). The variation of temperature and density as well as the variation of system pressure with respect to time were closely monitored for each case. The heat flux normal to the solid surface was also calculated to illustrate the effectiveness of heat transfer for hydrophilic and hydrophobic surfaces in cases of both nanostructured surface and flat surface. The results obtained show that both the wetting condition of the surface and the presence of internal recesses have significant effect on normal evaporation and explosive boiling of the thin liquid film. The heat transfer from solid to liquid in cases of surface with recesses are higher compared to flat surface without recesses. Also the surface with higher wettability (hydrophilic) provides more favorable conditions for boiling than the low-wetting surface (hydrophobic) and therefore, liquid argon responds quickly and shifts from liquid to vapor phase faster in case of hydrophilic surface. The heat transfer rate is also much higher in case of hydrophilic surface.
Molecular dynamics (MD) simulations have been performed to investigate the boiling phenomena of thin liquid film adsorbed on a nanostructured solid surface with particular emphasis on the effect of wetting condition of the solid surface. The molecular system consists of liquid and vapor argon, and solid platinum wall. The nanostructures which reside on top of the solid wall have shape of rectangular block. The solid-liquid interfacial wettability, in other words whether the solid surface is hydrophilic or hydrophobic has been altered for different cases to examine its effect on boiling phenomena. The initial configuration of the simulation domain comprised a three phase system (solid platinum, liquid argon and vapor argon) which was equilibrated at 90 K. After equilibrium period, the wall temperature was suddenly increased from 90 K to 250 K which is far above the critical point of argon and this initiates rapid or explosive boiling. The spatial and temporal variation of temperature and density as well as the variation of system pressure with respect to time were closely monitored for each case. The heat flux normal to the solid surface was also calculated to illustrate the effectiveness of heat transfer for different cases of wetting conditions of solid surface. The results show that the wetting condition of surface has significant effect on explosive boiling of the thin liquid film. The surface with higher wettability (hydrophilic) provides more favorable conditions for boiling than the low-wetting surface (hydrophobic) and therefore, liquid argon responds quickly and shifts from liquid to vapor phase faster in case of hydrophilic surface.
While it has long been recognized that bi-directional interaction between the heart and the vasculature plays a critical role in the proper functioning of the cardiovascular system, a comprehensive study of this interaction has largely been hampered by a lack of modeling framework capable of simultaneously accommodating high-resolution models of the heart and vasculature. Here, we address this issue and present a computational modeling framework that couples finite element (FE) models of the left ventricle (LV) and aorta to elucidate ventricular-arterial coupling in the systemic circulation. We show in a baseline simulation that the framework predictions of (1) LV pressure-volume loop, (2) aorta pressure-diameter relationship, (3) pressure-waveforms of the aorta, LV, and left atrium (LA) over the cardiac cycle are consistent with the physiological measurements found in healthy human. To develop insights of ventricular-arterial interactions, the framework was then used to simulate how alterations in the geometrical or, material parameter(s) of the aorta affect the LV and vice versa. We show that changing the geometry and microstructure of the aorta model in the framework led to changes in the functional behaviors of both LV and aorta that are consistent with experimental observations. On the other hand, changing contractility and passive stiffness of the LV model in the framework also produced changes in both the LV and aorta functional behaviors that are consistent with physiology principles.
Pulmonary arterial hypertension (PAH) is a complex disease involving increased resistance in the pulmonary arteries and subsequent right ventricular (RV) remodeling. Ventricular-arterial interactions are fundamental to PAH pathophysiology but are rarely captured in computational models. It is important to identify metrics that capture and quantify these interactions to inform our understanding of this disease as well as potentially facilitate patient stratification. Towards this end, we developed and calibrated two multi-scale high-resolution closed-loop computational models using open-source software: a high-resolution arterial model implemented using CRIMSON, and a high-resolution ventricular model implemented using FEniCS. Models were constructed with clinical data including non-invasive imaging and invasive hemodynamic measurements from a cohort of pediatric PAH patients. A contribution of this work is the discussion of inconsistencies in anatomical and hemodynamic data routinely acquired in PAH patients. We proposed and implemented strategies to mitigate these inconsistencies, and subsequently use this data to inform and calibrate computational models of the ventricles and large arteries. Computational models based on adjusted clinical data were calibrated until the simulated results for the high-resolution arterial models matched within 10% of adjusted data consisting of pressure and flow, whereas the high-resolution ventricular models were calibrated until simulation results matched adjusted data of volume and pressure waveforms within 10%. A statistical analysis was performed to correlate numerous data-derived and model-derived metrics with clinically assessed disease severity. Several model-derived metrics were strongly correlated with clinically assessed disease severity, suggesting that computational models may aid in assessing PAH severity.
