Valentin Krinsky

Low-energy control of electrical turbulence in the heart

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 ρ(E) and a characteristic time, τ, for tissue depolarization that obeys the power law τ ∝ Eα. 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.

Termination of Atrial Fibrillation Using Pulsed Low-Energy Far-Field Stimulation

Background— Electrically based therapies for terminating atrial fibrillation (AF) currently fall into 2 categories: antitachycardia pacing and cardioversion. Antitachycardia pacing uses low-intensity pacing stimuli delivered via a single electrode and is effective for terminating slower tachycardias but is less effective for treating AF. In contrast, cardioversion uses a single high-voltage shock to terminate AF reliably, but the voltages required produce undesirable side effects, including tissue damage and pain. We propose a new method to terminate AF called far-field antifibrillation pacing, which delivers a short train of low-intensity electric pulses at the frequency of antitachycardia pacing but from field electrodes. Prior theoretical work has suggested that this approach can create a large number of activation sites (“virtual” electrodes) that emit propagating waves within the tissue without implanting physical electrodes and thereby may be more effective than point-source stimulation. Methods and Results— Using optical mapping in isolated perfused canine atrial preparations, we show that a series of pulses at low field strength (0.9 to 1.4 V/cm) is sufficient to entrain and subsequently extinguish AF with a success rate of 93% (69 of 74 trials in 8 preparations). We further demonstrate that the mechanism behind far-field antifibrillation pacing success is the generation of wave emission sites within the tissue by the applied electric field, which entrains the tissue as the field is pulsed. Conclusions— AF in our model can be terminated by far-field antifibrillation pacing with only 13% of the energy required for cardioversion. Further studies are needed to determine whether this marked reduction in energy can increase the effectiveness and safety of terminating atrial tachyarrhythmias clinically.

INTERACTION OF ROTATING WAVES IN AN ACTIVE-CHEMICAL MEDIUM

Abstract The interaction of autowave sources is experimentally studied in an active chemical medium with excitable kinetics. Three types of vortices are considered: 1) A spiral wave (S) rotating in a simply-connected medium, 2) A spiral wave rotating around a hole (SH); and 3) A spiral wave (SN) with topological charge N. It is found that S synchronizes SH (except very small holes), and spiral waves with lower topological charge synchronize those with higher topological charge. It is also found that the interaction of autowave sources displays some unique properties because of their ability to appear on inhomogeities, to vanish and to move in the medium. A new phenomen of induced drift of spiral waves is demonstrated. The drift was induced by high-frequency concentrational waves propagating in the medium. A similar drift is observed upon interaction of vortices. The mechanism of the induced drift is explained in terms of wave-break translocation from one wave to another. Using this effect, one can control the location of wave sources in an active medium.

Models of defibrillation of cardiac tissue.

Heterogeneities, such as gap junctions, defects in periodical cellular lattices, intercellular clefts and fiber curvature allow one to understand the effect of an electric field in cardiac tissue. They induce membrane potential variations even in the bulk of the myocardium, with a characteristic sawtooth shape. The sawtooth potential, induced by heterogeneities at large scales (tissue strands) can be more easily observed, and lead to stronger effects than the one induced at the cellular level. In the generic model of propagation in cardiac tissue (FitzHugh), 4 mechanisms of defibrillation were found, two mechanisms based on excitation (E(A),E(M)), and two-on de-excitation (D(A),D(M)). The lowest electric field is required by an E(M) mechanism. In the Beeler-Reuter ionic model, mechanism D(M) is impossible. We critically review the experimental basis of the theory and propose new experiments. (c) 1998 American Institute of Physics.

How does an electric field defibrillate cardiac muscle

Abstract Cardiac fibrillation is caused by an irregular wave propagation. Fibrillation can be eliminated by a strong electric field (5 kV, 20 A, 2 msec). The mechanism of this phenomenon (defibrillation) is not known. The principal difficulty, as shown in experiments and confirmed by classical cable theory, is that the changes in transmembrane potential, e , induced by electric field, decay exponentially with distance from the electrodes. We study wave suppression by an electric field in generic excitable media. In excitable media consisting of separate cells (similar to biological tissues), we have found a suppression of rotating waves and defibrillation induced by strong electric field, contrary to what happens in continuous media. We show that the spatially periodic component of e which arises in cellular media is responsible for defibrillation. We have found that (i) it does not decay with distance; (ii) it can excite quiescent cells and terminate excitation in excited cells; (iii) the coupling between cardiac cells is a crucial parameter affecting the amplitude of the spatially periodic component of e , and the efficiency of defibrillation. New experiments on cardiac muscle are proposed.

Wave-train-induced termination of weakly anchored vortices in excitable media.

A free vortex in excitable media can be displaced and removed by a wave train. However, simple physical arguments suggest that vortices anchored to large inexcitable obstacles cannot be removed similarly. We show that unpinning of vortices attached to obstacles smaller than the core radius of the free vortex is possible through pacing. The wave-train frequency necessary for unpinning increases with the obstacle size and we present a geometric explanation of this dependence. Our model-independent results suggest that decreasing excitability of the medium can facilitate pacing-induced removal of vortices in cardiac tissue.

Phase-resolved analysis of the susceptibility of pinned spiral waves to far-field pacing in a two-dimensional model of excitable media

Life-threatening cardiac arrhythmias are associated with the existence of stable and unstable spiral waves. Termination of such complex spatio-temporal patterns by local control is substantially limited by anchoring of spiral waves at natural heterogeneities. Far-field pacing (FFP) is a new local control strategy that has been shown to be capable of unpinning waves from obstacles. In this article, we investigate in detail the FFP unpinning mechanism for a single rotating wave pinned to a heterogeneity. We identify qualitatively different phase regimes of the rotating wave showing that the concept of vulnerability is important but not sufficient to explain the failure of unpinning in all cases. Specifically, we find that a reduced excitation threshold can lead to the failure of unpinning, even inside the vulnerable window. The critical value of the excitation threshold (below which no unpinning is possible) decreases for higher electric field strengths and larger obstacles. In contrast, for a high excitation threshold, the success of unpinning is determined solely by vulnerability, allowing for a convenient estimation of the unpinning success rate. In some cases, we also observe phase resetting in discontinuous phase intervals of the spiral wave. This effect is important for the application of multiple stimuli in experiments.

Far field pacing supersedes anti-tachycardia pacing in a generic model of excitable media

Removing anchored spirals from obstacles is an important step in terminating cardiac arrhythmia. Conventional anti-tachycardia pacing (ATP) has this ability, but only under very restrictive conditions. In a generic model of excitable media, we demonstrate that for unpinning spiral waves from obstacles this profound limitation of ATP can be overcome by far field pacing (FFP). More specifically, an argument is presented for why FFP includes and thus can only extend the capabilities of ATP in the configurations considered. By numerical simulations, we show that in the model there exists a parameter region in which unpinning is possible by FFP but not by ATP. The relevance of this result regarding clinical applications is discussed.

Spiral wave drift induced by stimulating wave trains

We investigate the drift of a spiral wave core in a homogeneous excitable medium under the influence of a periodic stimulation by wave trains close to the core. Two important results were found. First, as opposed to existing theories of spiral wave drift, we observe drift induced by wave trains with periods larger than the period of the freely rotating spiral wave. Second, when investigating the drift of meandering spirals we found that the property of meandering of spirals is not robust against periodic stimulations. Simple phenomenological arguments are provided to explain these observations. (c) 2001 American Institute of Physics.

Effect of an externally applied electric field on excitation propagation in the cardiac muscle

Classical theory of potential distribution in cardiac muscle (cable theory) postulates that all effects of electric field (internally or externally applied) should decay exponentially with a space constant of the order of the tissue space constant ( approximately 1 mm). Classical theory does not take into account the cellular structure of the heart. Here, we formulate a mathematical model of excitation propagation taking into account cellular gap junctions. Investigation of the model has shown that the classical description is correct on the macroscopic scale only. At microscopic scale, electric field is modulated with a spatial period equal to the cell size (Plonsey and Barr), with the zero average. A very important new feature found here is that this effect of electric field does not decay at arbitrary big distances from the electrode. It opens the new way to control the excitation propagation in the cardiac muscle. In particular, we show that electric field can modify the velocity of propagation of an impulse in cardiac tissue at arbitrary big distances from electrode. In 2-dimensions, it can make rotating waves drift. To test these predictions, experiments with cardiac preparations are proposed.