Cellular and Ionic Mechanisms Underlying Arrhythmogenesis

Antzelevitch, Charles; Burashnikov, Alexander; Diego, José M. Di

doi:10.1007/978-1-59259-362-0_11

Cited by 4 publications

(3 citation statements)

References 246 publications

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“…Because the triangulation affects mainly the phase 2 of the AP, one might expect that the early phase of the T-wave might be the most affected as we observed using our ERD x% indices. The interval between the T-wave apex and the T-wave end may reflect the global transmural voltage dispersion demonstrated to be an important component of the genesis of TdPs in an experimental model [16]. Our results suggest that the late part of the T-wave, measured either by the TpTe interval or the LRD x% parameters, is more significantly prolonged in patients with history of TdPs than the individuals without arrhythmia.…”

Section: Discussionsupporting

confidence: 57%

Investigating the role of ventricular repolarization morphology in surface ECGs for identifying patients with a history of drug-induced arrhythmias

Couderc

Kääb

Hinterseer

et al. 2007

2007 Computers in Cardiology

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Assessing the propensity of an individual to druginduced arrhythmias when exposed to a QT-prolonging drug is challenging because baseline QT prolongation has limited predictive value. In this study, we investigated the role of computerized ECG parameters quantifying Twave morphology for the identification of individuals who developed drug-induced torsades de pointes (TdPs). In 34 patients, 5-minute digital ECGs have been acquired at baseline and during sotalol challenge. Seventeen of these patients had a history of drug-induced TdPs. We identified specific baseline features of the Twaves common to patients with history of TdPs. The sotalol-induced changes of T-wave morphologies were also different between the two groups suggesting that ECGs may provide relevant information for the identification of patients with an increased propensity toTdPs.

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Section: Discussionsupporting

confidence: 57%

Investigating the role of ventricular repolarization morphology in surface ECGs for identifying patients with a history of drug-induced arrhythmias

Couderc

Kääb

Hinterseer

et al. 2007

2007 Computers in Cardiology

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“…Of note, ventricular transmural repolarization heterogeneity is known to be involved in the generation of arrhythmias in a variety of syndromes, including the long and short QT syndromes, Brugada syndrome. 30 The apparent spatial dispersion of repolarization observed during coarse AF (between CT and adjacent regions; Fig. 4) may be important for the maintenance of coarse AF.…”

Section: Discussionmentioning

confidence: 98%

Role of Repolarization Restitution in the Development of Coarse and Fine Atrial Fibrillation in the Isolated Canine Right Atria

Burashnikov

Antzelevitch

2005

Cardiovasc electrophysiol

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Introduction: Although the role of action potential duration restitution (APD-R) in the initiation and maintenance of ventricular fibrillation (VF) has been the subject of numerous investigations, its role in the generation of atrial fibrillation (AF) is less well studied. The cellular and ionic basis for coarse versus fine AF is not well delineated. Methods and Results: We measured APD-R during acetylcholine-mediated AF as well as during pacing (standard and dynamic protocols) in crista teriminalis, pectinate muscle, superior vena cava, and appendage of isolated canine arterially perfused right atria (n = 15). Transmembrane action potential (TAP), pseudo-ECG, and isometric tension development were simultaneously recorded. Acetylcholine flattened APD-R measured by both standard and dynamic protocols, but promoted induction of AF. AF was initially coarse, converting to fine within 3-15 minutes of AF. Coarse, but not fine AF was associated with dramatic fluctuations in tension development, reflecting wide variations in intracellular calcium activity ([Ca 2+ ] i ). During coarse AF, APD-R data displayed a cloud-like distribution pattern, with a wide range of maximum APD-R slope (from 1.21 to 0.35). A maximum APD-R slope >1 was observed only in crista terminalis (3/10). The APD-R relationship was relatively linear and flat during fine AF. Reduction of [Ca 2+ ] i was associated with fine AF whereas augmentation of [Ca 2+ ] i with coarse AF. Conclusions: Our data indicate that while APD-R may have a limited role in the maintenance of coarse AF, it is unlikely to contribute to the maintenance of fine AF and that [Ca 2+ ] i dynamics determine the degree to which AF is coarse or fine.

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“…A large number of previous studies (Karagueuzian et al, 1993 ; Lee et al, 1996 ; Koller et al, 1998 , 2000 ; Taggart et al, 2003 ; Pak et al, 2004 ) have associated alternans with steeply sloping restitution curves relating APD to the preceding DI (Nolasco and Dahlen, 1968 ). Furthermore, such steeply sloping restitution curves have been associated with arrhythmogenicity in humans with the Brugada syndrome (Narayan et al, 2007 ), another hereditary arrhythmic syndrome (Antzelevitch et al, 2003 ). Furthermore, similar associations have been made in murine genetic models of both the Brugada syndrome and the congenital long-QT syndrome type 3, as well as in hypokalemic murine hearts (Sabir et al, 2008a , b ).…”

Section: Discussionmentioning

confidence: 99%

Alternans in Genetically Modified Langendorff-Perfused Murine Hearts Modeling Catecholaminergic Polymorphic Ventricular Tachycardia

Sabir

Jones

et al. 2010

Front. Physiology

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The relationship between alternans and arrhythmogenicity was studied in genetically modified murine hearts modeling catecholaminergic polymorphic ventricular tachycardia (CPVT) during Langendorff perfusion, before and after treatment with catecholamines and a β-adrenergic antagonist. Heterozygous (RyR2p/s) and homozygous (RyR2s/s) RyR2-P2328S hearts, and wild-type (WT) controls, were studied before and after treatment with epinephrine (100 nM and 1 μM) and propranolol (100 nM). Monophasic action potential recordings demonstrated significantly greater incidences of arrhythmia in RyR2p/s and RyR2s/s hearts as compared to WTs. Arrhythmogenicity in RyR2s/s hearts was associated with alternans, particularly at short baseline cycle lengths. Both phenomena were significantly accentuated by treatment with epinephrine and significantly diminished by treatment with propranolol, in full agreement with clinical expectations. These changes took place, however, despite an absence of changes in mean action potential durations, ventricular effective refractory periods or restitution curve characteristics. Furthermore pooled data from all hearts in which arrhythmia occurred demonstrated significantly greater alternans magnitudes, but similar restitution curve slopes, to hearts that did not demonstrate arrhythmia. These findings thus further validate the RyR2-P2328S murine heart as a model for human CPVT, confirming an alternans phenotype in common with murine genetic models of the Brugada syndrome and the congenital long-QT syndrome type 3. In contrast to these latter similarities, however, this report demonstrates the dissociation of alternans from changes in the properties of restitution curves for the first time in a murine model of a human arrhythmic syndrome.

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Cellular and Ionic Mechanisms Underlying Arrhythmogenesis

Cited by 4 publications

References 246 publications

Investigating the role of ventricular repolarization morphology in surface ECGs for identifying patients with a history of drug-induced arrhythmias

Investigating the role of ventricular repolarization morphology in surface ECGs for identifying patients with a history of drug-induced arrhythmias

Role of Repolarization Restitution in the Development of Coarse and Fine Atrial Fibrillation in the Isolated Canine Right Atria

Alternans in Genetically Modified Langendorff-Perfused Murine Hearts Modeling Catecholaminergic Polymorphic Ventricular Tachycardia

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