Effect of intercellular conductance and stimuli coupling interval on reentrant arrhythmia
04 Jun 2015-pp 1-2
TL;DR: It is observed from the simulations that premature excitation of the tissue in presence of an ischemic zone can act as a substrate to induce sustained reentrant arrhythmias and these reentries are generated only within a limited window of reduced coupling intervals.
Abstract: Arrhythmia generation post ischemia has been linked to loss of cell-to-cell electrical interaction. Arrhythmias like ventricular fibrillation and tachycardia manifest as reentrant circuits at the tissue level. In this paper, a discrete venticular myocyte network of 100×100 cells interconnected using gap junction conductances is simulated along with an ischemic inclusion to study the wave patterns that arise from the ischemic zone due to varied coupling intervals of the stimulus. It is observed from the simulations that premature excitation of the tissue in presence of an ischemic zone can act as a substrate to induce sustained reentrant arrhythmias. Also, these reentrant wave patterns are generated only within a limited window of reduced coupling intervals.
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TL;DR: A new version of the human ventricular cell model is developed, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics, which concludes that steepAPD restitution-mediated instability is a potential mechanism for VF in the human heart.
Abstract: Ventricular fibrillation (VF) is one of the main causes of death in the Western world. According to one hypothesis, the chaotic excitation dynamics during VF are the result of dynamical instabilities in action potential duration (APD) the occurrence of which requires that the slope of the APD restitution curve exceeds 1. Other factors such as electrotonic coupling and cardiac memory also determine whether these instabilities can develop. In this paper we study the conditions for alternans and spiral breakup in human cardiac tissue. Therefore, we develop a new version of our human ventricular cell model, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics. We apply this model to study the conditions for electrical instability in single cells, for reentrant waves in a ring of cells, and for reentry in two-dimensional sheets of ventricular tissue. We show that an important determinant for the onset of instability is the recovery dynamics of the fast sodium current. Slower sodium current recovery leads to longer periods of spiral wave rotation and more gradual conduction velocity restitution, both of which suppress restitution-mediated instability. As a result, maximum restitution slopes considerably exceeding 1 (up to 1.5) may be necessary for electrical instability to occur. Although slopes necessary for the onset of instabilities found in our study exceed 1, they are within the range of experimentally measured slopes. Therefore, we conclude that steep APD restitution-mediated instability is a potential mechanism for VF in the human heart.
1,012 citations
"Effect of intercellular conductance..." refers methods in this paper
...Each cell’s action potential is simulated using the electrophysiological properties of the Ten Tusscher-Panfilov human ventricular myocyte model [7]....
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TL;DR: Data indicate that Ib arrhythmias and ECG changes during ischemia are influenced by the loss of cell-to-cell electrical interaction, which contributes to failure of impulse propagation in the setting of altered tissue excitability as a result of elevated [K+]e and low pHe.
Abstract: Background This study was designed to test the hypothesis that the loss of cell-to-cell electrical interaction during ischemia modulates the amplitude of ischemia-induced TQ-segment depression (ie, the injury potential) and the occurrence of ventricular fibrillation (VF) during the so-called Ib phase of ventricular arrhythmias. Methods and Results Regional ischemia was induced by 60 minutes of mid–left anterior descending coronary artery ligation in open-chest swine (n=10). Cell-to-cell electrical uncoupling was defined as the onset of the terminal rise in whole-tissue resistivity (Rt). Local activation times and TQ-segment changes (injury potential) were determined from unipolar electrograms. Extracellular K+ ([K+]e) and pH (pHe) were measured with plunge-wire ion-selective electrodes. VF occurred in 6 of 10 pigs during regional no-flow ischemia between 19 and 30 minutes after the arrest of perfusion. The occurrence of VF was positively correlated to the onset of cell-to-cell electrical uncoupling (R2=.8...
227 citations
TL;DR: There is, even in the era of implantable cardiac defibrillators, need for further understanding the mechanism of ischemia-induced VF, and whether either accelerated uncoupling or maintenance of gap junctional communication is antiarrhythmic.
Abstract: Sudden cardiac death forms a major cause of mortality. Myocardial ischemia-induced ventricular fibrillation (VF) is frequently the underlying mechanism. Ventricular arrhythmias arise in two distinct phases during the first hour of ischemia. The first, the 1A phase, has been extensively studied, and few studies relate to the 1B phase. The latter is associated with intercellular electrical uncoupling, mediated by decreased conductance of gap junction channels. Although the relation between gap junctional uncoupling and decreased conduction velocity appears clear under normoxic conditions, additional factors contribute to conduction slowing during ischemia, and VF occurs preferentially at moderate levels of uncoupling. A potential mechanism of arrhythmias depends on temporary electrotonic depression of intrinsically viable tissue by the large bulk of the ischemic zone. This causes conduction slowing and conduction block in the surviving layers, leading to arrhythmias. These arrhythmias then resolve with progression of uncoupling. It is unknown whether either accelerated uncoupling or maintenance of gap junctional communication is antiarrhythmic. Ischemic preconditioning postpones both gap junctional uncoupling and occurrence of VF. Given the burden of sudden death and the large number of casualties in the low-risk population, there is, even in the era of implantable cardiac defibrillators, need for further understanding the mechanism of ischemia-induced VF.
140 citations
"Effect of intercellular conductance..." refers background in this paper
...The second phase (1B) occurs after 20 - 45 minutes and has been associated with intercellular electrical uncoupling by decreasing the conductance of the gap junction channels [2]....
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TL;DR: The study suggests that the initiation of ischemia-induced 1b arrhythmias is related to LV wall stress, which is less frequent and less severe than in working preparations.
82 citations
"Effect of intercellular conductance..." refers background in this paper
...preferentially from the ischemic border as a consequence of mechanical stretch exerted by the surrounding myocardium on the ischemic region [3]....
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TL;DR: In this article, a phase of intermediate coupling between surviving epicardium and inexcitable midmyocardium underlies 1B arrhythmias was found to be a substrate for ventricular fibrillation.
Abstract: Objective: Acute ischemia comes with two phases of life-threatening arrhythmias, early (within 10 minutes, 1A) and late (after about 15 minutes, 1B). The mechanism of the latter is unknown and in this paper, we test the hypothesis that a phase of intermediate coupling between surviving epicardium and inexcitable midmyocardium underlies 1B arrhythmias. Methods: Pig hearts ( n = 26) were retrogradely perfused with a blood Tyrode's mixture. The left anterior descending artery was occluded. We investigated (1) inducibility of ventricular fibrillation (VF) with programmed stimulation, (2) tissue impedance (Rt) heterogeneity within the ischemic zone, (3) multiple subepicardial and midmyocardial electrograms, (4) subepicardial lactate dehydrogenase (LDH) and glycogen content. Results: In nine of ten hearts, one—three premature stimuli caused VF between 14 and 53 min of ischemia. This typically happened when the Rt of the ischemic zone had increased up to 40% of its final value. More uncoupling terminated the period of VF inducibility. The excitability of the surviving subepicardial layer was depressed during the same period with partial uncoupling, but recovered when the uncoupling from the midmyocardium had progressed further. Conclusions: We show that 1B-VF can be induced within a distinct time window and coincides with a distinct range of Rt rise. Subepicardium is electrically depressed, presumably through coupling with midmyocardium, complete uncoupling causes subepicardial recovery and terminates the substrate for 1B-VF. Hence, we suggest that the substrate for 1B-VF consists of intermediate coupling of subepicardium and midmyocardium.
70 citations