Cellular Basis for Trigger and Maintenance of Ventricular Fibrillation in the Brugada Syndrome Model

Aiba, Takeshi; Shimizu, Wataru; Hidaka, Ichiro; Uemura, Kazunori; Noda, Takashi; Zheng, Can; Kamiya, Atsunori; Inagaki, Masumi; Sugimachi, Masaru; Sunagawa, Kenji

doi:10.1016/j.jacc.2005.12.064

Cited by 123 publications

(94 citation statements)

References 37 publications

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“…This has been linked to an increased risk of cardiac death [151] and, in particular, to a higher risk of arrhythmogenicity in short QT, long QT and Brugada syndromes [152][153][154][155]. In Brugada syndrome, for instance, dispersion of repolarization is thought to be caused by an abbreviation of the APD of the right ventricular epicardium due to loss of the action potential dome [156]. Then, a region of depolarized tissue (during calcium current entrance, or phase-2 of the AP) can re-excite adjacent regions that exhibit shorter action potential duration (APD) [130], producing an extrasystole which can eventually initate phase-2 reentry (see Figure 17).…”

Section: Gradients Of Electrophysiological Propertiesmentioning

confidence: 99%

Nonlinear physics of electrical wave propagation in the heart: a review

2016

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Abstract. The beating of the heart is a synchronized contraction of muscle cells (myocytes) that are triggered by a periodic sequence of electrical waves (action potentials) originating in the sino-atrial node and propagating over the atria and the ventricles. Cardiac arrhythmias like atrial and ventricular fibrillation (AF,VF) or ventricular tachycardia (VT) are caused by disruptions and instabilities of these electrical excitations, that lead to the emergence of rotating waves (VT) and turbulent wave patterns (AF,VF). Numerous simulation and experimental studies during the last 20 years have addressed these topics. In this review we focus on the nonlinear dynamics of wave propagation in the heart with an emphasis on the theory of pulses, spirals and scroll waves and their instabilities in excitable media and their application to cardiac modeling. After an introduction into electrophysiological models for action potential propagation, the modeling and analysis of spatiotemporal alternans, spiral and scroll meandering, spiral breakup and scroll wave instabilities like negative line tension and sproing are reviewed in depth and discussed with emphasis on their impact in cardiac arrhythmias.

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Section: Gradients Of Electrophysiological Propertiesmentioning

confidence: 99%

Nonlinear physics of electrical wave propagation in the heart: a review

2016

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“…4,15 A large increase in TDR is likely to be arrhythmogenic because the dispersion of repolarization and refractoriness occurs over a very short distance (the width of the ventricular wall), creating a steep repolarization gradient. 16,17 It is the steepness of the repolarization gradient rather than the total magnitude of dispersion that determines its arrhythmogenic potential. Apicobasal or interventricular dispersion of repolarization is less informative because it may or may not be associated with a steep repolarization gradient and thus may or may not be associated with arrhythmic risk.…”

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Does Tpeak–Tend provide an index of transmural dispersion of repolarization?

Antzelevitch¹,

Sicouri²,

Diego³

et al. 2007

Heart Rhythm

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Differences in the time course of repolarization of the three predominant myocardial cell types have been shown to contribute to the inscription of the T wave of the electrocardiogram (ECG). Voltage gradients developing as a result of the different time course of repolarization of phases 2 and 3 in the three cell types give rise to opposing voltage gradients on either side of the M region, which are in part responsible for the inscription of the T wave. 1 In the case of an upright T wave, the epicardial response is the earliest to repolarize and the M cell action potential is the latest. In the coronary-perfused wedge preparation, repolarization of the epicardial action potential coincides with the peak of the T wave and repolarization of the M cells is coincident with the end of the T wave, so that the interval from the peak to the end of the T wave provides a measure of transmural dispersion of repolarization (TDR).Based on these early studies, the Tpeak-Tend interval in precordial ECG leads was suggested to provide an index of transmural dispersion of repolarization. 2 More recent studies have also provided guidelines for the estimation of transmural dispersion of repolarization in the case of more complex T waves, including negative, biphasic and triphasic T waves. 3 In such cases, the interval from the nadir of the first component of the T wave to the end of the T wave was shown to provide an electrocardiographic approximation of TDR.While these relationships are relatively straight forward in the coronary-perfused wedge preparation, extrapolation to the surface ECG recorded in vivo must be approached with great caution and will require careful validation. The Tpeak-Tend interval is unlikely to provide an absolute measure of transmural dispersion in vivo, as elegantly demonstrated by Xia and coworkers 4 . However, changes in this parameter are thought to be capable of reflecting changes in spatial dispersion of repolarization, particularly TDR, and thus may be prognostic of arrhythmic risk under a variety of conditions. 5-10 Takenaka et al. recently demonstrated exercise-induced accentuation of the Tpeak-Tend interval in LQT1 patients, but not LQT2. 9

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“…15) The cellular basis of Brugada syndrome has been attributed to depression or loss of the action potential dome in the RV epicardium, which creates a transmural voltage gradient that is responsible for the ST-segment elevation in Brugada syndrome and repolarization heterogeneity of the RV. 26,27) It was also shown in dogs that extrasystolic activity due to phase 2 reentry can arise in the intact wall of the right ventricle and serve as the trigger for ventricular tachycardia/VF. 27,28) Clinical studies on the pathogenesis of Brugada syndrome also revealed the presence of a deeply notched action potential in the RV epicardium and abnormal RV action potential restitution properties.…”

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confidence: 99%

Abnormal Atrial Repolarization and Depolarization Contribute to the Inducibility of Atrial Fibrillation in Brugada Syndrome

et al. 2010

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SummaryBrugada syndrome is often accompanied by atrial tachyarrhythmia, such as atrial fibrillation (AF). The aim of this study was to examine atrial vulnerability in patients with Brugada syndrome. Two groups of patients were compared: 18 patients with Brugada syndrome (Brugada syndrome group) and 11 age-matched patients with neither organic heart disease nor AF episodes (control group). Programmed electrical stimulation was performed from the right atrium (RA), and the effective refractory period of the right atrium (ERP-RA), interatrial conduction time (IACT), monophasic action potentials (MAPs) at the high RA, and the inducibility of AF lasting > 30 seconds were studied. MAP duration at 80% repolarization (MAPD 80 ) was calculated. AF was induced with a single extrastimulus or double extrastimuli in all patients with Brugada syndrome but in none of the control patients. The ERP-RA did not differ between the groups. IACT at the shortest diastolic interval was significantly increased in the Brugada syndrome group compared to that in the control group. The maximum slope of the MAPD 80 restitution curve was significantly steeper in the Brugada syndrome group than in the control group (2.4 ± 2.0 versus 0.82 ± 0.36, P < 0.02). Ventricular fibrillation was induced with ventricular programmed stimulation in all Brugada syndrome patients. Both abnormal interatrial conduction and steep restitution of action potential duration may contribute to the atrial arrhythmogenicity in Brugada syndrome. (Int Heart J 2010; 51: 159-165)

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Cellular Basis for Trigger and Maintenance of Ventricular Fibrillation in the Brugada Syndrome Model

Abstract: Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.

Cited by 123 publications

References 37 publications

Nonlinear physics of electrical wave propagation in the heart: a review

Nonlinear physics of electrical wave propagation in the heart: a review

Does Tpeak–Tend provide an index of transmural dispersion of repolarization?

Abnormal Atrial Repolarization and Depolarization Contribute to the Inducibility of Atrial Fibrillation in Brugada Syndrome

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