Low-energy control of electrical turbulence in the heart.
ABSTRACT: Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult, because of the nonlinear interaction of excitation waves in a heterogeneous anatomical substrate. In the absence of a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation. Here we establish the relationship between the response of the tissue to an electric field and the spatial distribution of heterogeneities in the scale-free coronary vascular structure. We show that in response to a pulsed electric field, E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density ?(E) and a characteristic time, ?, for tissue depolarization that obeys the power law ????E(?). These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. We show in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore, efficient termination of fibrillation. Using this control strategy, we demonstrate low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques.
Project description:Clinically, cardiac fibrillation caused by spiral and turbulent waves can be terminated by globally resetting electric activity in cardiac tissues with a single high-voltage electric shock, but it is usually associated with severe side effects. Presently, a promising alternative uses wave emission from heterogeneities induced by a sequence of low-voltage uniform electric field pulses. Nevertheless, this method can only emit waves locally near obstacles in turbulent waves and thereby requires multiple obstacles to globally synchronize myocardium and thus to terminate fibrillation. Here we propose a new approach using wave emission from heterogeneities induced by a low-voltage circularly polarized electric field (i.e., a rotating uniform electric field). We find that, this approach can generate circular wave trains near obstacles and they propagate outwardly. We study the characteristics of such circular wave trains and further find that, the higher-frequency circular wave trains can effectively suppress spiral turbulence.
Project description:Spirals or scroll waves pinned to heterogeneities in cardiac tissues may cause lethal arrhythmias. To unpin these life-threatening spiral waves, methods of wave emission from heterogeneities (WEH) induced by low-voltage pulsed DC electric fields (PDCEFs) and circularly polarized electric fields (CPEFs) have been used in two-dimensional (2D) cardiac tissues. Nevertheless, the unpinning of scroll waves in three-dimensional (3D) cardiac systems is much more difficult than that of spiral waves in 2D cardiac systems, and there are few reports on the removal of pinned scroll waves in 3D cardiac tissues by electric fields. In this article, we investigate in detail the removal of pinned scroll waves in a generic model of 3D excitable media using PDCEF, AC electric field (ACEF) and CPEF, respectively. We find that spherical waves can be induced from the heterogeneities by these electric fields in initially quiescent excitable media. However, only CPEF can induce spherical waves with frequencies higher than that of the pinned scroll wave. Such higher-frequency spherical waves induced by CPEF can be used to drive the pinned scroll wave out of the cardiac systems. We hope this remarkable ability of CPEF can provide a better alternative to terminate arrhythmias caused by pinned scroll waves.
Project description:Multiple unstable spiral waves rotating around phase singularities (PSs) in the heart, i.e., ventricular fibrillation (VF), is the leading cause of death in the industrialized world. Spiral waves are ubiquitous in nature and have been extensively studied by physiologists, mathematicians, chemists, and biologists, with particular emphasis on their movement and stability. Spiral waves are not easy to terminate because of the difficulty of "breaking" the continuous spatial progression of phase around the PSs. The only means to stop VF (i.e., cardiac defibrillation) is to deliver a strong electric shock to the heart. Here, we use the similarities between spiral wave dynamics and limit cycle oscillators to characterize the spatio-temporal dynamics of VF and defibrillation via phase-resetting curves. During VF, only PSs, including their formation and termination, were associated with large phase changes. At low shock strengths, phase-resetting curves exhibited characteristics of weak (type 1) resetting. As shock strength increased, the number of postshock PSs decreased to zero coincident with a transition to strong (type 0) resetting. Our results indicate that shock-induced spiral wave termination in the heart is caused by altering the phase around the PSs, such that, depending on the preshock phase, sites are either excited by membrane depolarization (phase advanced) or exhibit slowed membrane repolarization (phase delay). Strong shocks that defibrillate break the continuity of phase around PSs by forcing the state of all sites to the fast portion of state space, thus quickly leading to a "homogeneity of state," subsequent global repolarization and spiral wave termination.
Project description:Defining mechanisms for cardiac fibrillation is challenging because, in contrast to other arrhythmias, fibrillation exhibits complex non-repeatability in spatiotemporal activation but paradoxically exhibits conserved spatial gradients in rate, dominant frequency, and electrical propagation. Unlike animal models, in which fibrillation can be mapped at high spatial and temporal resolution using optical dyes or arrays of contact electrodes, mapping of cardiac fibrillation in patients is constrained practically to lower resolutions or smaller fields-of-view. In many animal models, atrial fibrillation is maintained by localized electrical rotors and focal sources. However, until recently, few studies had revealed localized sources in human fibrillation, so that the impact of mapping constraints on the ability to identify rotors or focal sources in humans was not described. Here, we determine the minimum spatial and temporal resolutions theoretically required to detect rigidly rotating spiral waves and focal sources, then extend these requirements for spiral waves in computer simulations. Finally, we apply our results to clinical data acquired during human atrial fibrillation using a novel technique termed focal impulse and rotor mapping (FIRM). Our results provide theoretical justification and clinical demonstration that FIRM meets the spatio-temporal resolution requirements to reliably identify rotors and focal sources for human atrial fibrillation.
Project description:We propose a solution to a long-standing problem: how to terminate multiple vortices in the heart, when the locations of their cores and their critical time windows are unknown. We scan the phases of all pinned vortices in parallel with electric field pulses (E-pulses). We specify a condition on pacing parameters that guarantees termination of one vortex. For more than one vortex with significantly different frequencies, the success of scanning depends on chance, and all vortices are terminated with a success rate of less than one. We found that a similar mechanism terminates also a free (not pinned) vortex. A series of about 500 experiments with termination of ventricular fibrillation by E-pulses in pig isolated hearts is evidence that pinned vortices, hidden from direct observation, are significant in fibrillation. These results form a physical basis needed for the creation of new effective low energy defibrillation methods based on the termination of vortices underlying fibrillation.
Project description:Chaotic spiral or scroll wave dynamics can be found in diverse systems. In cardiac dynamics, spiral or scroll waves of electrical excitation determine the dynamics during life-threatening arrhythmias like ventricular fibrillation. In numerical studies it was found that chaotic episodes of spiral and scroll waves can be transient, thus they terminate spontaneously. We show in this study that this behavior can also be observed using models which describe the ion channel dynamics of human cardiomyocytes (Bueno-Orovio-Cherry-Fenton model and the Ten Tusscher-Noble-Noble-Panfilov model). For both models we find that the average lifetime of the chaotic transients grows exponentially with the system size. With this behavior, we classify the systems into the group of type-II supertransients. We observe a significant difference of the breakup behavior between the models, which results in a distinct dynamics during the final phase just before the termination. The observation of a (temporally) stable single-spiral state affects the prevailing description of the dynamics of type-II supertransients as being "quasi-stationary" and also the feasibility of predicting the spontaneous termination of the spiral wave dynamics. In the long term, the relation between the breakup behavior of spiral waves and properties of chaotic transients like predictability or average transient lifetime may contribute to an improved understanding and classification of cardiac arrhythmias.
Project description:The mechanisms underlying ventricular fibrillation (VF) are not well understood. The electrical activity on the heart surface during VF has been recorded extensively in the experimental setting and in some cases clinically; however, corresponding transmural activation patterns are prohibitively difficult to measure. In this paper, we use a high-resolution biventricular heart model to study three-dimensional electrical activity during fibrillation, focusing on the driving sources of VF: "filaments," the organising centres of unstable reentrant scroll waves. We show, for the first time, specific 3D filament dynamics during simulated VF in a whole heart geometry that includes fine-scale anatomical structures. Our results suggest that transmural activity is much more complex than what would be expected from surface observations alone. We present examples of complex intramural activity, including filament breakup and reattachment, anchoring to the thin right ventricular apex; rapid transitions among various filament shapes; and filament lengths much greater than wall thickness. We also present evidence for anatomy playing a major role in VF development and coronary vessels and trabeculae influencing filament dynamics. Overall, our results indicate that intramural activity during simulated VF is extraordinarily complex and suggest that further investigation of 3D filaments is necessary to fully comprehend recorded surface patterns.
Project description:Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength--electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely.
Project description:Localized heterogeneities, caused by the regional proliferation of fibroblasts, occur in mammalian hearts because of diseases like myocardial infarction. Such fibroblast clumps can become sources of pathological reentrant activities, e.g., spiral or scroll waves of electrical activation in cardiac tissue. The occurrence of reentry in cardiac tissue with heterogeneities, such as fibroblast clumps, can depend on the frequency at which the medium is paced. Therefore, it is important to study the reentry-initiating potential of such fibroblast clumps at different frequencies of pacing. We investigate the arrhythmogenic effects of fibroblast clumps at high- and low-frequency pacing. We find that reentrant waves are induced in the medium more prominently at high-frequency pacing than with low-frequency pacing. We also study the other factors that affect the potential of fibroblast clumps to induce reentry in cardiac tissue. In particular, we show that the ability of a fibroblast clump to induce reentry depends on the size of the clump, the distribution and percentage of fibroblasts in the clump, and the excitability of the medium. We study the process of reentry in two-dimensional and a three-dimensional mathematical models for cardiac tissue.
Project description:Spiral waves anchored to obstacles in cardiac tissues may cause lethal arrhythmia. To unpin these anchored spirals, comparing to high-voltage side-effect traditional therapies, wave emission from heterogeneities (WEH) induced by the uniform electric field (UEF) has provided a low-voltage alternative. Here we provide a new approach using WEH induced by the circularly polarized electric field (CPEF), which has higher success rate and larger application scope than UEF, even with a lower voltage. And we also study the distribution of the membrane potential near an obstacle induced by CPEF to analyze its mechanism of unpinning. We hope this promising approach may provide a better alternative to terminate arrhythmia.