Bidomain Predictions of Virtual Electrode-Induced Make and Break Excitations around Blood Vessels

Abstract

Introduction and backgroundVirtual electrodes formed by field stimulation during defibrillation of cardiac tissue play an important role in eliciting activations. It has been suggested that the coronary vasculature is an important source of virtual electrodes, especially during low-energy defibrillation. This work aims to further the understanding of how virtual electrodes from the coronary vasculature influence defibrillation outcomes.MethodsUsing the bidomain model, we investigated how field stimulation elicited activations from virtual electrodes around idealized intramural blood vessels. Strength–interval curves, which quantify the stimulus strength required to elicit wavefront propagation from the vessels at different states of tissue refractoriness, were computed for each idealized geometry.ResultsMake excitations occurred at late diastolic intervals, originating from regions of depolarization around the vessel. Break excitations occurred at early diastolic intervals, whereby the vessels were able to excite surrounding refractory tissue due to the local restoration of excitability by virtual electrode-induced hyperpolarizations. Overall, strength–interval curves had similar morphologies and underlying excitation mechanisms compared with previous experimental and numerical unipolar stimulation studies of cardiac tissue. Including the presence of the vessel wall increased the field strength required for make excitations but decreased the field strength required for break excitations, and the field strength at which break excitations occurred was generally greater than 5 V/cm. Finally, in a more realistic ventricular slice geometry, the proximity of virtual electrodes around subepicardial vessels was seen to cause break excitations in the form of propagating unstable wavelets to the subepicardial layer.ConclusionRepresenting the blood vessel wall microstructure in computational bidomain models of defibrillation is recommended as it significantly alters the electrophysiological response of the vessel to field stimulation. Although vessels may facilitate excitation of relatively refractory tissue via break excitations, the field strength required for this is generally greater than those used in the literature on low-energy defibrillation. However, the high-intensity shocks used in standard defibrillation may elicit break excitation propagation from the coronary vasculature.

Ventricular Endocardial Tissue Geometry Affects Stimulus Threshold and Effective Refractory Period

“…Although cathodal make excitation was the main mechanism of capture seen in these simulations, break excitation effects—in which the regions of depolarization under the anode initially conduct through the newly made regions of hyperpolarization under the anode upon stimulus cessation—would be more prominent when the stimulus is applied at increasing stages of refractoriness (at higher strengths than applied here). The interaction between regions of de- and hyperpolarization induced by the bipolar electrode has important synergies with other studies examining direct unipolar stimulation ( 37 ) by an insulated plunge electrode ( 38 ) or incorporating the effects of local tissue injury ( 39 ), as well as by application of a 9-V battery ( 40 ), in addition to far-field virtual electrodes induced around fine-scale anatomical structures such as intramural clefts ( 41 ) and blood vessels ( 17 , 27 , 42 , 43 ).…”

“…Experimentally, the stimulus voltage was gradually increased until the tissue showed entrainment at a pacing cycle length of 1 s, with successful capture being confirmed by the appearance of a subsequent (pseudo-) QRS complex on the ECG. Computationally, the threshold stimulus (the minimal stimulus strength required to elicit wavefront propagation) was calculated using a bisection algorithm ( 27 ), with a tolerance of less than 0.01 V.…”

“…Strength-interval curves were computed using a similar approach to the capture threshold and ERP analysis, above ( 27 ). Specifically, a single paced beat (S1) was initiated in each computational model, using a stimulus strength equal to the previously computed capture threshold.…”

Extended Bidomain Modeling of Defibrillation: Quantifying Virtual Electrode Strengths in Fibrotic Myocardium

“…Virtual electrodes are thought to underlie local shifts of transmembrane voltages and thus trigger action potentials and elicit wave fronts that interfere with fibrillation. Recent work using computational modeling focused on understanding virtual electrodes caused by vessels (Connolly et al, 2017a,b) and related curvature of the surface of tissue heterogeneities to myocyte depolarization and initiation of wave fronts (Bittihn et al, 2012).…”