Using a computational model of a coupled reaction-diffusion-mechanics system, we find that mechanical deformation can induce automatic pacemaking activity. Pacemaking is shown to occur after a single electrical or mechanical stimulus in an otherwise nonoscillatory medium. We study the mechanisms underpinning this effect and conditions for its existence. We show that self-organized pacemakers drift throughout the medium to approach attractors with locations that depend on the size of the medium, and on the location of the initial stimulus.

Rotating spiral waves organize excitation in various biological, physical, and chemical systems. They underpin a variety of important phenomena, such as cardiac arrhythmias, morphogenesis processes, and spatial patterns in chemical reactions. Important insights into spiral wave dynamics have been obtained from theoretical studies of the reaction–diffusion (RD) partial differential equations. However, most of these studies have ignored the fact that spiral wave rotation is often accompanied by substantial deformations of the medium. Here, we show that joint consideration of the RD equations with the equations of continuum mechanics for tissue deformations (RD–mechanics systems), yield important effects on spiral wave dynamics. We show that deformation can induce the breakup of spiral waves into complex spatiotemporal patterns. We also show that mechanics leads to spiral wave drift throughout the medium approaching dynamical attractors, which are determined by the parameters of the model and the size of the medium. We study mechanisms of these effects and discuss their applicability to the theory of cardiac arrhythmias. Overall, we demonstrate the importance of RD–mechanics systems for mathematics applied to life sciences.

Keldermann RH, Nash MP, Gelderblom H, Wang VY, Panfilov AV. Electromechanical wavebreak in a model of the human left ventricle. Am J Physiol Heart Circ Physiol 299: H134 -H143, 2010. First published April 16, 2010; doi:10.1152/ajpheart.00862.2009In the present report, we introduce an integrative three-dimensional electromechanical model of the left ventricle of the human heart. Electrical activity is represented by the ionic TP06 model for human cardiac cells, and mechanical activity is represented by the NiedererHunter-Smith active contractile tension model and the exponential Guccione passive elasticity model. These models were embedded into an anatomic model of the left ventricle that contains a detailed description of cardiac geometry and the fiber orientation field. We demonstrated that fiber shortening and wall thickening during normal excitation were qualitatively similar to experimental recordings. We used this model to study the effect of mechanoelectrical feedback via stretch-activated channels on the stability of reentrant wave excitation. We found that mechanoelectrical feedback can induce the deterioration of an otherwise stable spiral wave into turbulent wave patterns similar to that of ventricular fibrillation. We identified the mechanisms of this transition and studied the three-dimensional organization of this mechanically induced ventricular fibrillation. ventricular fibrillation; computer simulations; mechanics; electrophysiology; mechanoelectrical feedback; stretch-activated channels MECHANICAL ACTIVITY of the heart is initiated by electrical waves of excitation that propagate through the heart and initiate cardiac contraction. Abnormal excitation of the heart may result in cardiac arrhythmias and the loss of mechanical pump function, leading to sudden cardiac death. Sudden cardiac death caused by cardiac arrhythmias is the most common cause of death in the industrialized world, and, in most cases, this is due to ventricular fibrillation (VF) (73). It has been shown in clinical and experimental studies (11,17,26,41,46,62,68,70) that VF occurs as a result of the onset of turbulent electrical activation patterns of the heart that are underpinned by multiple reentrant sources of excitation. Mechanisms behind the onset of reentrant sources in the heart and processes resulting in breakup of these sources into complex turbulent activation patterns are of great interest, e.g., in the design of therapeutic strategies to prevent or treat cardiac arrhythmias.One of the important factors that affects electrical excitation of the heart is mechanoelectrical feedback. It has been shown that mechanical deformation alters the electrical properties of myocytes via stretch-activated channels (59), which can change the shape of the action potential in response to stretch (34, 37). Mechanoelectric feedback has been studied in the clinical community for well over a century (for reviews, see Refs. 34,37,38) and may have both proarrhythmic and antiarrhythmic consequences. However, the mechanisms underlying these ph...

The onset of ventricular fibrillation (VF) has been associated with steep action potential duration restitution in both clinical and computational studies. Recently, detailed clinical restitution properties in cardiac patients were reported showing a substantial degree of heterogeneity in restitution slopes at the epicardium of the ventricles. The aim of the present study was to investigate the effect of heterogeneous restitution properties in a three-dimensional model of the ventricles using these clinically measured restitution data. We used a realistic model of the human ventricles, including detailed descriptions of cell electrophysiology, ventricular anatomy, and fiber direction anisotropy. We extended this model by mapping the clinically observed epicardial restitution data to our anatomic representation using a diffusion-based algorithm. Restitution properties were then fitted by regionally varying parameters of the electrophysiological model. We studied the effects of restitution heterogeneity on the organization of VF by analyzing filaments and the distributions of excitation periods. We found that the number of filaments and the excitation periods were both dependent on the extent of heterogeneity. An increased level of heterogeneity leads to a greater number of filaments and a broader distribution of excitation periods, thereby increasing the complexity and dynamics of VF. Restitution heterogeneity may play an important role in providing a substrate for cardiac arrhythmias.

Sudden cardiac death is one of the major causes of death in the industrialized world. It is most often caused by a cardiac arrhythmia called ventricular fibrillation (VF). Despite its large social and economical impact, the mechanisms for VF in the human heart yet remain to be identified. Two of the most frequently discussed mechanisms observed in experiments with animal hearts are the multiple wavelet and mother rotor hypotheses. Most recordings of VF in animal hearts are consistent with the multiple wavelet mechanism. However, in animal hearts, mother rotor fibrillation has also been observed. For both multiple wavelet and mother rotor VF, cardiac heterogeneity plays an important role. Clinical data of action potential restitution measured from the surface of human hearts have been recently published. These in vivo data show a substantial degree of spatial heterogeneity. Using these clinical restitution data, we studied the dynamics of VF in the human heart using a heterogeneous computational model of human ventricles. We hypothesized that this observed heterogeneity can serve as a substrate for mother rotor fibrillation. We found that, based on these data, mother rotor VF can occur in the human heart and that ablation of the mother rotor terminates VF. Furthermore, we found that both mother rotor and multiple wavelet VF can occur in the same heart depending on the initial conditions at the onset of VF. We studied the organization of these two types of VF in terms of filament numbers, excitation periods, and frequency domains. We conclude that mother rotor fibrillation is a possible mechanism in the human heart.