Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software.
Alternans of action potential duration has been associated with T wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i) Alternans predominantly develops first on the endocardium. (ii) The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii) In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv) Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v) The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared to those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicates some underlying predisposition to chaos and can help to guide the design of new drugs and devices controlling and preventing arrhythmic events.
We investigate the interaction of intracellular calcium spatio-temporal variations with the self-sustained contractions in cardiac myocytes. A consistent mathematical model is presented considering a hyperelastic description of the passive mechanical properties of the cell, combined with an active-strain framework to explain the active shortening of myocytes and its coupling with cytosolic and sarcoplasmic calcium dynamics. A finite element method based on a Taylor-Hood discretization is employed to approximate the nonlinear elasticity equations, whereas the calcium concentration and mechanical activation variables are discretized by piecewise linear finite elements. Several numerical tests illustrate the ability of the model in predicting key experimentally established characteristics including: (i) calcium propagation patterns and contractility, (ii) the influence of boundary conditions and cell shape on the onset of structural and active anisotropy and (iii) the high localized stress distributions at the focal adhesions. Besides, they also highlight the potential of the method in elucidating some important subcellular mechanisms affecting, e.g. cardiac repolarization.Keywords: cardiomyocyte modelling; active-strain contraction; nonlinear elasticity; calcium propagation; finite element formulation; coupled multiphysics.
Thermal effects affecting spatiotemporal behavior of cardiac tissue are discussed by relating temperature variations to proarrhythmic dynamics in the heart. By introducing a thermoelectric coupling in a minimal model of cardiac tissue, we are able to reproduce experimentally measured dynamics obtained simultaneously from epicardial and endocardial canine right ventricles at different temperatures. A quantitative description of emergent proarrhythmic properties of restitution, conduction velocity, and alternans regimes as a function of temperature is presented. Complex discordant alternans patterns that enhance tissue dispersion consisting of one wave front and three wave backs are described in both simulations and experiments. Possible implications for model generalization are finally discussed.
Paralytic ileus is a temporary syndrome with impairment of peristalsis and no passage of food through the intestine. Although improvements in supportive measures have been achieved, no therapy useful to specifically reduce or eliminate the motility disorder underlying postoperative ileus has been developed yet. In this paper, we draw a plausible, physiologically fine-tuned scenario, which explains a possible cause of paralytic ileus. To this aim we extend the existing 1D intestinal electrophysiological Aliev-Richards-Wikswo ionic model based on a double-layered structure in two and three dimensions. Thermal coupling is introduced here to study the influence of temperature gradients on intestine tissue which is an important external factor during surgery. Numerical simulations present electrical spiral waves similar to those experimentally observed already in the heart, brain and many other excitable tissues. This fact seems to suggest that such peculiar patterns, here electrically and thermally induced, may play an important role in clinically experienced disorders of the intestine, then requiring future experimental analyses in the search for possible implications for medical and physiological practice and bioengineering.
The activity of pancreatic β cells can be described by biological networks of coupled nonlinear oscillators that, via electrochemical synchronization, release insulin in response to augmented glucose levels. In this work, we analyze the emergent behavior of regular and percolated β-cells clusters through a stochastic mathematical model where "functional" networks arise. We show that the emergence and robustness of the synchronized dynamics depend both on intrinsic and extrinsic parameters. In particular, cellular noise level, glucose concentration, network spatial architecture, and cell-to-cell coupling strength are the key factors for the generation of a rhythmic and robust activity. Their role in the functional network topology associated with β-cells clusters is analyzed and discussed.
We propose a new model to describe diffusion processes within active deformable media. Our general theoretical framework is based on physical and mathematical considerations, and it suggests to use diffusion tensors directly coupled to mechanical stress. A proof-of-concept experiment and the proposed generalised reaction-diffusion-mechanics model reveal that initially isotropic and homogeneous diffusion tensors turn into inhomogeneous and anisotropic quantities due to the intrinsic structure of the nonlinear coupling. We study the physical properties leading to these effects, and investigate mathematical conditions for its occurrence. Together, the experiment, the model, and the numerical results obtained using a mixed-primal finite element method, clearly support relevant consequences of stress-assisted diffusion into anisotropy patterns, drifting, and conduction velocity of the resulting excitation waves. Our findings also indicate the applicability of this novel approach in the description of mechano-electrical feedback in actively deforming bio-materials such as the heart.
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