Increased Temporo-Spatial Dispersion of Repolarization During Double Premature Stimulation in the Intact Ventricle

Ventricular arrhythmias, consisting of single ectopic beats (sEB), multiple EB (mEB), and Torsades de Pointes (TdP, defined as >5 beats with QRS vector twisting around isoelectric line) can be induced in the anesthetized chronic AV-block (CAVB) dog by dofetilide (IKr-blocker). The interplay between temporal dispersion of repolarization, quantified as short-term variability (STV), and spatial dispersion of repolarization (SDR) in the initiation and perpetuation of these arrhythmias remains unclear. Five inducible (>3 TdPs/10') CAVB dogs were observed for 10' from the start of dofetilide infusion (0.025mg/kg, 5'). An intracardiac decapolar electrogram (EGM) catheter and 30 intramural cardiac needles in the left ventricle (LV) were introduced. STVARI was derived from 31 consecutive activation recovery intervals (ARI) on the intracardiac EGM, using the formula: . The mean SDR3D in the LV was determined as the three-dimensional repolarization time differences between the intramural cardiac needles. Moments of measurement included baseline (BL) and after dofetilide infusion prior to first 1) sEB (occurrence at 100±35"), 2) mEB (224±96"), and 3) non self-terminating TdP (454±298"). STVARI increased from 2.15±0.32ms at BL to 3.73±0.99ms* prior to the first sEB and remained increased without further significant progression to mEB (4.41±0.45ms*) and TdP (5.07±0.84ms*) (*p<0.05 compared to BL). SDR3D did not change from 31±11ms at BL to 43±13ms prior to sEB, but increased significantly prior to mEB (68±7ms*) and to TdP (86±9ms*+) (+p<0.05 compared to sEB). An increase in STV contributes to the initiation of sEB whereas an increase in SDR is important for the perpetuation of non self-terminating TdPs.

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The effects of nifekalant hydrochloride on the spatial dispersion of repolarization after direct current defibrillation in patients with oral amiodarone and β-blocker therapy

Journal of Arrhythmia ◽

10.1016/j.joa.2013.05.009 ◽

2014 ◽

Vol 30 (3) ◽

pp. 150-156

Author(s):

Keiko Maeda ◽

Masahiko Takagi ◽

Hiroaki Tatsumi ◽

Eiichiro Nakagawa ◽

Minoru Yoshiyama

Keyword(s):

Direct Current ◽

Spatial Dispersion ◽

Blocker Therapy ◽

Dispersion Of Repolarization ◽

Β Blocker

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Regional upregulation of Kv2.1-encoded current,I K,slow2, in Kv1DN mice is abolished by crossbreeding with Kv2DN mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00576.2002 ◽

2003 ◽

Vol 284 (2) ◽

pp. H491-H500 ◽

Cited By ~ 42

Author(s):

Jun Zhou ◽

Sodikdjon Kodirov ◽

Mitsunobu Murata ◽

Peter D. Buckett ◽

Jeanne M. Nerbonne ◽

...

Keyword(s):

Potassium Current ◽

Spatial Dispersion ◽

Ventricular Myocytes ◽

Delayed Rectifier ◽

Inactivation Kinetics ◽

Electrical Remodeling ◽

Programmed Electrical Stimulation ◽

Dispersion Of Repolarization ◽

Pharmacological Studies ◽

Prolonged Action Potential Duration

Overexpression of a truncated Kv1.1 channel transgene in the heart (Kv1DN) resulted in mice with a prolonged action potential duration due to marked attenuation of a rapidly activating, slowly inactivating potassium current ( I K,slow1) in ventricular myocytes. Optical mapping and programmed electrical stimulation revealed inducible ventricular tachycardia due to spatial dispersion of repolarization and refractoriness. Here we show that a delayed rectifier with slower inactivation kinetics ( I K,slow2) was selectively upregulated in Kv1DN cardiocytes. This electrical remodeling was spatially restricted to myocytes derived from the apex of the left ventricle. Biophysical and pharmacological studies of I K,slow2 indicate that it resembles Kv2-encoded currents. Northern blot analyses and real-time PCR revealed upregulation of Kv2.1 transcript in Kv1DN mice. Crossbreeding of Kv1DN mice with mice expressing a truncated Kv2.1 polypeptide (Kv2DN) eliminated I K,slow2. In summary, our data indicate that the spatially restrictive upregulation of Kv2.1-encoded currents underlies the increased dispersion of the repolarization observed in Kv1DN mice.

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Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00355.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. H2024-H2038 ◽

Cited By ~ 166

Author(s):

Charles Antzelevitch

Keyword(s):

Sudden Cardiac Death ◽

Cardiac Death ◽

Spatial Dispersion ◽

Ventricular Myocardium ◽

Polymorphic Ventricular Tachycardia ◽

Long Qt ◽

Dispersion Of Repolarization ◽

Qt Syndrome ◽

Transmural Dispersion

This review examines the role of spatial electrical heterogeneity within the ventricular myocardium on the function of the heart in health and disease. The cellular basis for transmural dispersion of repolarization (TDR) is reviewed, and the hypothesis that amplification of spatial dispersion of repolarization underlies the development of life-threatening ventricular arrhythmias associated with inherited ion channelopathies is evaluated. The role of TDR in long QT, short QT, and Brugada syndromes, as well as catecholaminergic polymorphic ventricular tachycardia (VT), is critically examined. In long QT syndrome, amplification of TDR is often secondary to preferential prolongation of the action potential duration (APD) of M cells; in Brugada syndrome, however, it is thought to be due to selective abbreviation of the APD of the right ventricular epicardium. Preferential abbreviation of APD of the endocardium or epicardium appears to be responsible for the amplification of TDR in short QT syndrome. In catecholaminergic polymorphic VT, reversal of the direction of activation of the ventricular wall is responsible for the increase in TDR. In conclusion, long QT, short QT, Brugada, and catecholaminergic polymorphic VT syndromes are pathologies with very different phenotypes and etiologies, but they share a common final pathway in causing sudden cardiac death.

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Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model

Frontiers in Physiology ◽

10.3389/fphys.2021.642083 ◽

2021 ◽

Vol 12 ◽

Author(s):

Valerie Y. H. van Weperen ◽

Albert Dunnink ◽

Alexandre Bossu ◽

Jet D. M. Beekman ◽

Veronique M. F. Meijborg ◽

...

Keyword(s):

Spatial Dispersion ◽

Torsade De Pointes ◽

Left Ventricular ◽

Dispersion Of Repolarization ◽

Dog Model ◽

Severe Bradycardia ◽

Idioventricular Rhythm ◽

Surface Electrocardiogram ◽

Temporal Dispersion ◽

Unipolar Electrograms

IntroductionTorsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP.MethodsDofetilide (25 μg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions. Recordings included surface electrocardiogram and short-term variability (STV) of repolarization from endocardial unipolar electrograms. TdP inducibility (three or more episodes within 10 min after start of dofetilide) and arrhythmic activity scores (AS) were established. Mapping experiments in 10 additional dogs determined the effect of lowering rate on STV and spatial dispersion of repolarization (SDR) in baseline.ResultsIVR-tested animals had longer baseline RR-interval (1,403 ± 271 ms) and repolarization intervals than RVA60 animals. Dofetilide increased STV similarly under both rhythm strategies. Nevertheless, TdP inducibility and AS were higher under IVR conditions (6/8 and 37 ± 27 vs. 1/8 and 8 ± 12 in RVA60, respectively, both p < 0.05). Mapping: Pacing from high (128 ± 10 bpm) to middle (88 ± 10 bpm) to experimental rate (61 ± 3 bpm) increased all electrophysiological parameters, including interventricular dispersion, due to steeper left ventricular restitution curves, and intraventricular SDR: maximal cubic dispersion from 60 ± 14 (high) to 69 ± 17 (middle) to 84 ± 22 ms (p < 0.05 vs. high and middle rate).ConclusionIn CAVB dogs, severe bradycardia increases the probability and severity of arrhythmic events by heterogeneously causing electrophysiological instability, which is mainly reflected in an increased spatial, and to a lesser extent temporal, dispersion of repolarization.

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