How Hyperpolarization and the Recovery of Excitability Affect Propagation through a Virtual Anode in the Heart

Charteris, Nicholas; Roth, Bradley J.

doi:10.1155/2011/375059

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…The conduction velocity is large in the virtual anode; rapid propagation through a virtual anode is thought to be one mechanism for the upper limit of vulnerability. 7 The wave front and conduction velocity profile are reproduced for the area around the virtual electrode as shown in Figs. 9 and S2.…”

Section: Resultsmentioning

confidence: 99%

A Simplified Approach for Simultaneous Measurements of Wavefront Velocity and Curvature in the Heart Using Activation Times

Mazeh

Haines

Kay

et al. 2013

Cardiovasc Eng Tech

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The velocity and curvature of a wave front are important factors governing the propagation of electrical activity through cardiac tissue, particularly during heart arrhythmias of clinical importance such as fibrillation. Presently, no simple computational model exists to determine these values simultaneously. The proposed model uses the arrival times at four or five sites to determine the wave front speed (v), direction (θ), and radius of curvature (ROC) (r0). If the arrival times are measured, then v, θ, and r0 can be found from differences in arrival times and the distance between these sites. During isotropic conduction, we found good correlation between measured values of the ROC r0 and the distance from the unipolar stimulus (r = 0.9043 and p < 0.0001). The conduction velocity (m/s) was correlated (r = 0.998, p < 0.0001) using our method (mean = 0.2403, SD = 0.0533) and an empirical method (mean = 0.2352, SD = 0.0560). The model was applied to a condition of anisotropy and a complex case of reentry with a high voltage extra stimulus. Again, results show good correlation between our simplified approach and established methods for multiple wavefront morphologies. In conclusion, insignificant measurement errors were observed between this simplified approach and an approach that was more computationally demanding. Accuracy was maintained when the requirement that ε (ε = b/r0, ratio of recording site spacing over wave fronts ROC) was between 0.001 and 0.5. The present simplified model can be applied to a variety of clinical conditions to predict behavior of planar, elliptical, and reentrant wave fronts. It may be used to study the genesis and propagation of rotors in human arrhythmias and could lead to rotor mapping using low density endocardial recording electrodes.

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Section: Resultsmentioning

confidence: 99%

A Simplified Approach for Simultaneous Measurements of Wavefront Velocity and Curvature in the Heart Using Activation Times

Mazeh

Haines

Kay

et al. 2013

Cardiovasc Eng Tech

Self Cite

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“…Moreover, sequential light pulses can be applied repetitively, as charging of capacitors to generate ICD electrical shocks is not required. The flexibility of using spatially and temporally shaped light patterns for defibrillation could also be used to minimize secondary pro-arrhythmic effects, which are discussed to be a major cause for electrical defibrillation failure (Charteris and Roth, 2011).…”

Section: Clinical Implications Of Optogenetic Defibrillationmentioning

confidence: 99%

Optogenetic Termination of Cardiac Arrhythmia: Mechanistic Enlightenment and Therapeutic Application?

et al. 2019

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Optogenetic methods enable selective de- and hyperpolarization of cardiomyocytes expressing light-sensitive proteins within the myocardium. By using light, this technology provides very high spatial and temporal precision, which is in clear contrast to electrical stimulation. In addition, cardiomyocyte-specific expression would allow pain-free stimulation. In light of these intrinsic technical advantages, optogenetic methods provide an intriguing opportunity to understand and improve current strategies to terminate cardiac arrhythmia as well as for possible pain-free arrhythmia termination in patients in the future. In this review, we give a concise introduction to optogenetic stimulation of cardiomyocytes and the whole heart and summarize the recent progress on optogenetic defibrillation and cardioversion to terminate cardiac arrhythmia. Toward this aim, we specifically focus on the different mechanisms of optogenetic arrhythmia termination and how these might influence the prerequisites for success. Furthermore, we critically discuss the clinical perspectives and potential patient populations, which might benefit from optogenetic defibrillation devices.

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“…These so-called virtual electrodes (Wikswo et al, 1995) consist of a virtual cathode with depolarization in a dog bone shape (Akar et al, 2001) and a perpendicular virtual anode with hyperpolarization parallel to the fiber orientation (Knisley, 1995; Neunlist and Tung, 1995; Sambelashvili et al, 2003) which can be even larger than the virtual cathode (Nikolski et al, 2004). For decades successful defibrillation has only been attributed to the depolarized tissue while the hyperpolarization is considered to generate new wavefronts by a anode-break mechanism (Cranefield et al, 1957) or create a phase singularity which can trigger a new excitation and generate a new arrhythmic wavefront (Efimov et al, 1998; Roth, 1998; Charteris and Roth, 2011). However, the specific effects of hyperpolarization in the intact heart could not be addressed experimentally so far because it is impossible to predict or control the extent of the virtual electrodes induced by electrical field stimulation.…”

Section: Introductionmentioning

confidence: 99%

Optogenetic Hyperpolarization of Cardiomyocytes Terminates Ventricular Arrhythmia

et al. 2019

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Cardiac defibrillation to terminate lethal ventricular arrhythmia (VA) is currently performed by applying high energy electrical shocks. In cardiac tissue, electrical shocks induce simultaneously de- and hyperpolarized areas and only depolarized areas are considered to be responsible for VA termination. Because electrical shocks do not allow proper control over spatial extent and level of membrane potential changes, the effects of hyperpolarization have not been explored in the intact heart. In contrast, optogenetic methods allow cell type-selective induction of de- and hyperpolarization with unprecedented temporal and spatial control. To investigate effects of cardiomyocyte hyperpolarization on VA termination, we generated a mouse line with cardiomyocyte-specific expression of the light-driven proton pump ArchT. Isolated cardiomyocytes showed light-induced outward currents and hyperpolarization. Free-running VA were evoked by electrical stimulation of explanted hearts perfused with low K + and the K ATP channel opener Pinacidil. Optogenetic hyperpolarization was induced by epicardial illumination, which terminated VA with an average efficacy of ∼55%. This value was significantly higher compared to control hearts without illumination or ArchT expression ( p = 0.0007). Intracellular recordings with sharp electrodes within the intact heart revealed hyperpolarization and faster action potential upstroke upon illumination, which should fasten conduction. However, conduction speed was lower during illumination suggesting enhanced electrical sink by hyperpolarization underlying VA termination. Thus, selective hyperpolarization in cardiomyocytes is able to terminate VA with a completely new mechanism of increased electrical sink. These novel insights could improve our mechanistic understanding and treatment strategies of VA termination.

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How Hyperpolarization and the Recovery of Excitability Affect Propagation through a Virtual Anode in the Heart

Cited by 5 publications

References 30 publications

A Simplified Approach for Simultaneous Measurements of Wavefront Velocity and Curvature in the Heart Using Activation Times

A Simplified Approach for Simultaneous Measurements of Wavefront Velocity and Curvature in the Heart Using Activation Times

Optogenetic Termination of Cardiac Arrhythmia: Mechanistic Enlightenment and Therapeutic Application?

Optogenetic Hyperpolarization of Cardiomyocytes Terminates Ventricular Arrhythmia

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