Tunnel Propagation of Postshock Activations as a Hypothesis for Fibrillation Induction and Isoelectric Window

Abstract

Abstract-Comprehensive understanding of the ventricular response to shocks is the approach most likely to succeed in reducing defibrillation threshold. We propose a new theory of shock-induced arrhythmogenesis that unifies all known aspects of the response of the heart to monophasic (MS) and biphasic (BS) shocks. The central hypothesis is that submerged "tunnel" propagation of postshock activations through shock-induced intramural excitable areas underlies fibrillation induction and the existence of isoelectric window. We conducted simulations of fibrillation induction using a realistic bidomain model of rabbit ventricles. Following pacing, MS and BS of various strengths/timings were delivered. The results demonstrated that, during the isoelectric window, an activation originated deep within the ventricular wall, arising from virtual electrodes; it then propagated fully intramurally through an excitable tunnel induced by the shock, until it emerged onto the epicardium, becoming the earliest-propagated postshock activation. Differences in shock outcomes for MS and BS were found to stem from the narrower BS intramural postshock excitable area, often resulting in conduction block, and the difference in the mechanisms of origin of the postshock activations, namely intramural virtual electrode-induced phase singularity for MS and virtual electrode-induced propagated graded response for BS. This study provides a novel analysis of the 3D mechanisms underlying the origin of postshock activations in the process of fibrillation induction by MS and BS and the existence of isoelectric window. Comprehensive knowledge and appreciation of the mechanisms by which a shock interacts with the heart is the approach most likely to succeed in reducing shock energy.The presence of an isoelectric window (IW) following unsuccessful defibrillation attempts 3-5 led to the understanding that an electric shock terminates ongoing fibrillation but then reinitiates it; hence the mechanisms of fibrillation induction and its reinitiation (unsuccessful defibrillation) are the same. Indeed, striking similarities between these mechanisms have been found, particularly with regard to propagation of the first global postshock activation (PA) and IW duration. 4 -6 The similarity is supported by the significant correlation between upper limit of vulnerability (ULV) and DFT. 7,8 Therefore, elucidating the origin of PAs resulting in fibrillation induction is expected to provide invaluable insight into the mechanisms of defibrillation failure and could contribute significantly to the effort to find novel ways to appreciably lower DFT.Although numerous hypotheses 9 -12 exist for the mechanisms of PA origin, none provides comprehensive mechanistic explanation of the following findings:1. Earliest PA following near-ULV (or near-DFT) shocks occurred after the epicardium recovered completely from shock-induced direct excitation. 3,5 2. IW increased as shock strength increased. 4,6,13 3. For both monophasic (MS) and biphasic (BS) shock waveforms, earliest PAs a...

Modeling Defibrillation

“…APD can be either extended (by positive VEP) or shortened (by negative VEP) to a degree that depends on VEP magnitude and shock timing, with strong negative VEP completely abolishing (de-exciting) the action potential thus creating post-shock excitable gaps. As demonstrated in bidomain modeling studies (Ashihara et al, 2008;Roth, 1995), the post-shock VEP pattern is also the major determinant of the origin of post-shock activations. In those regions where shock-induced virtual anodes and virtual cathodes are in close proximity, a "break" excitation at shock-end (i.e, the "break" of the shock) can be elicited.…”

“…However, in a complex three-dimensional anatomical structure such as the heart electrical events occur throughout the entire myocardium including the depth of the myocardial walls. Therefore, the restricted capabilities of current optical mapping techniques to detect events which may occur in deeper layers of the myocardial wall without any signature at the surfaces (Ashihara et al, 2008), poses a severe limitation, rendering investigations of defibrillation mechanisms by experimental means alone a challenging endeavor.…”

“…FEM and FVM are both very well suited for spatial discretizations of complex geometries with smooth representations of the boundaries, which is a key feature when polarization patterns induced via extracellularly applied currents are to be studied. Both FVM and FEM have been used to model electrical activity in anatomical realistic models of the atria (Harrild & Henriquez, 2000;Seemann et al, 2006;Vigmond et al, 2004;Virag et al, 2002) as well as the ventricles (Ashihara et al, 2008;Plank et al, 2009;Potse et al, 2006;Ten Tusscher et al, 2007). Mesh generation requirements are similar for both techniques, that is, the domain of interest has to be tessellated into a set of non-overlapping and conformal geometric primitives (Fig.…”

“…In practice, a trade-off has to be made between accuracy and computational tractability. In tissue and organ scale modeling studies a standard choice for h, or for an average discretizationh when unstructured grids are considered, is 250µm, but finer ) as well as coarser discretizations (Ashihara et al, 2008;Saucerman et al, 2004) have been reported as well. With very coarse discretizations, h >500 µm, and physiologically realistic models of cellular dynamics simulations deviate substantially from results obtained at finer resolutions.…”

Cardiovascular Mechanics

“…Over the past few years, multi-scale computational models of ventricular electrical activity have been routinely used in numerous studies [106][107][108] where models have been discretized at a paracellular resolution [109,110] using highly detailed representations of cellular dynamics with integrated models of excitation-contraction coupling and mitochondrial energetics [111]. In comparison, a fairly small number of studies employed organ level models of ventricular cardiac mechanics, and, even less frequent, models of ventricular electromechanics.…”