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Alternans of cardiac action potential duration represent critical precursors for the development of life-threatening arrhythmias and sudden cardiac death. The system's thermal state affects these electrical disorders requiring additional theoretical and experimental efforts to improve a patient-specific clinical understanding. In such a scenario, we generalize a recent work from Loppini et al. [Phys. Rev. E 100, 020201(R) (2019)PREHBM2470-004510.1103/PhysRevE.100.020201] by performing an extended spatiotemporal correlation study. We consider high-resolution optical mapping recordings of canine ventricular wedges' electrical activity at different temperatures and pacing frequencies. We aim to recommend the extracted characteristic length as a potential predictive index of cardiac alternans onset and evolution within a wide range of system states. In particular, we show that a reduction of temperature results in a drop of the characteristic length, confirming the impact of thermal instabilities on cardiac dynamics. Moreover, we theoretically investigate the use of such an index to identify and predict different alternans regimes. Finally, we propose a constitutive phenomenological law linking conduction velocity, characteristic length, and temperature in view of future numerical investigations.

Complex spatiotemporal patterns of action potential duration have been shown to occur in many mammalian hearts due to period-doubling bifurcations that develop with increasing frequency of stimulation. Here, through high-resolution optical mapping experiments and mathematical modeling, we introduce a characteristic spatial length of cardiac activity in canine ventricular wedges via a spatiotemporal correlation analysis, at different stimulation frequencies and during fibrillation. We show that the characteristic length ranges from 40 to 20 cm during one-to-one responses and it decreases to a specific value of about 3 cm at the transition from period-doubling bifurcation to fibrillation. We further show that during fibrillation, the characteristic length is about 1 cm. Another significant outcome of our analysis is the finding of a constitutive phenomenological law obtained from a nonlinear fitting of experimental data which relates the conduction velocity restitution curve with the characteristic length of the system. The fractional exponent of 3/2 in our phenomenological law is in agreement with the domain size remapping required to reproduce experimental fibrillation dynamics within a realistic cardiac domain via accurate mathematical models.

This work reports the results of the theoretical investigation of nonlinear dynamics and spiral wave breakup in a generalized two-variable model of cardiac action potential accounting for thermo-electric coupling and diffusion nonlinearities. As customary in excitable media, the common Q 10 and Moore factors are used to describe thermo-electric feedback in a 10° range. Motivated by the porous nature of the cardiac tissue, in this study we also propose a nonlinear Fickian flux formulated by Taylor expanding the voltage dependent diffusion coefficient up to quadratic terms. A fine tuning of the diffusive parameters is performed a priori to match the conduction velocity of the equivalent cable model. The resulting combined effects are then studied by numerically simulating different stimulation protocols on a one-dimensional cable. Model features are compared in terms of action potential morphology, restitution curves, frequency spectra, and spatio-temporal phase differences. Two-dimensional long-run simulations are finally performed to characterize spiral breakup during sustained fibrillation at different thermal states. Temperature and nonlinear diffusion effects are found to impact the repolarization phase of the action potential wave with non-monotone patterns and to increase the propensity of arrhythmogenesis.

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., (© The Authors 2013. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.)

Aims: Hypothermia is well known to be pro-arrhythmic, yet it has beneficial effects as a resuscitation therapy and valuable during intracardiac surgeries. Therefore, we aim to study the mechanisms that induce fibrillation during hypothermia. A better understanding of the complex spatiotemporal dynamics of heart tissue as a function of temperature will be useful in managing the benefits and risks of hypothermia., Methods and Results: We perform two-dimensional numerical simulations by using a minimal model of cardiac action potential propagation fine-tuned on experimental measurements. The model includes thermal factors acting on the ionic currents and the gating variables to correctly reproduce experimentally recorded restitution curves at different temperatures. Simulations are implemented using WebGL, which allows long simulations to be performed as they run close to real time. We describe (i) why fibrillation is easier to induce at low temperatures, (ii) that there is a minimum size required for fibrillation that depends on temperature, (iii) why the frequency of fibrillation decreases with decreasing temperature, and (iv) that regional cooling may be an anti-arrhythmic therapy for small tissue sizes however it may be pro-arrhythmic for large tissue sizes., Conclusion: Using a mathematical cardiac cell model, we are able to reproduce experimental observations, quantitative experimental results, and discuss possible mechanisms and implications of electrophysiological changes during hypothermia.

Spiral waves in excitable biological media are associated with pathological situations. In the heart an action potential vortex pinned by an obstacle has to be removed through defibrillation protocols fine-tuned theoretically by using electrophysiological nonlinear mathematical models. Cardiac tissue, however, is an electroelastic medium whose electrical properties are strongly affected by large deformations. In this paper we specifically investigate the electroelastic pinning-unpinning mechanism in order to include cardiac contraction in the preexisting theoretically modeled defibrillation scenarios. Based on a two-dimensional minimal electromechanical model, we show numerically the existence of an unpinning band characterized by the size of the obstacle, the pacing site, and the frequency. Similar numerical simulations, performed in the absence of elastic coupling, show small differences in comparison with the electroelastic studies, suggesting for this specific scenario of pinning-unpinning dynamics a nonprominent role of elasticity.

We present an electromechanical model of myocardium tissue coupling a modified FitzHugh-Nagumo type system, describing the electrical activity of the excitable media, with finite elasticity, endowed with the capability of describing muscle contractions. The high degree of deformability of the medium makes it mandatory to set the diffusion process in a moving domain, thereby producing a direct influence of the deformation on the electrical activity. Various mechano-electric effects concerning the propagation of cylindrical waves, the rotating spiral waves, and the spiral breakups are discussed.

An extended Fitzhugh-Nagumo model including linear viscoelasticity is derived in general and studied in detail in the one-dimensional case. The equations of the theory are numerically integrated in two situations: (i) a free insulated fiber activated by an initial Gaussian distribution of action potential, and (ii) a clamped fiber stimulated by two counter phased currents, located at both ends of the space domain. The former case accounts for a description of the physiological experiments on biological samples in which a fiber contracts because of the spread of action potential, and then relaxes. The latter case, instead, is introduced to extend recent models discussing a strongly electrically stimulated fiber so that nodal structures associated on quasistanding waves are produced. Results are qualitatively in agreement with physiological behavior of cardiac fibers. Modifications induced on the action potential of a standard Fitzhugh-Nagumo model appear to be very small even when strong external electric stimulations are activated. On the other hand, elastic backreaction is evident in the model.