Electrophysiological determinants of arrhythmic susceptibility upon endocardial and epicardial pacing in guinea‐pig heart

Osadchii, Oleg E.

doi:10.1111/j.1748-1716.2012.02428.x

Cited by 6 publications

(10 citation statements)

References 38 publications

(58 reference statements)

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“…In contrast, epicardial pacing is associated with increased APD at epicardium, but reduced endocardial APD. Transmural APD dispersion therefore becomes greater when switching from epicardial to endocardial pacing (Osadchii 2012a: study II) . In line with these findings, optical mapping of repolarization in rabbit hearts has revealed that transmural APD patterns are strongly determined by the activation sequence; even though a positive endocardial‐to‐epicardial APD difference is invariably seen during endocardial pacing, the gradient is reversed when activation proceeds from the epicardium …”

Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 85%

“…In perfused guinea‐pig hearts, the inducibility of APD alternans and tachyarrhythmia is higher when electrical stimulations are applied at endocardium compared to epicardium, in both RV and LV chamber . Endocardial stimulations also require lower threshold current strength to induce VF.…”

Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 99%

“…A greater availability of Na + channels contributes to the recurrence of excitability at earlier time points during repolarization, as evidenced by a lower ERP‐to‐APD ratio determined at the endocardium compared to the epicardium in guinea‐pig heart (Osadchii 2012a: study II) . This ensures an increased window over which the LV can be re‐excited by a premature ectopic pulse, thus facilitating VT initiation at the endocardium.…”

Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 99%

“…Likewise, when a premature action potential is generated at earlier repolarization time points, it propagates with a longer conduction delay owing to incomplete recovery of I Na from inactivation. Accordingly, transmural conduction time is longer when extrasystolic stimulations are applied at the endocardium compared to the epicardium (Osadchii 2012a: study II), an effect that can facilitate re‐entry by reducing the excitation wavelength.…”

Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 99%

“…Finally, endocardial‐to‐epicardial difference in arrhythmic susceptibility could be explained by a steeper slope of APD rate adaptation at the endocardium. The minimum pacing interval that allows 1 : 1 LV capture is shorter during endocardial stimulations, which contributes to the increased slope of the initial steep portion of the restitution curve . The latter, according to the restitution hypothesis (see Section ), facilitates APD alternans and increases propensity to VF.…”

Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 99%

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Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Osadchii

2017

Acta Physiologica

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In cardiac patients, life-threatening tachyarrhythmia is often precipitated by abnormal changes in ventricular repolarization and refractoriness. Repolarization abnormalities typically evolve as a consequence of impaired function of outward K currents in cardiac myocytes, which may be caused by genetic defects or result from various acquired pathophysiological conditions, including electrical remodelling in cardiac disease, ion channel modulation by clinically used pharmacological agents, and systemic electrolyte disorders seen in heart failure, such as hypokalaemia. Cardiac electrical instability attributed to abnormal repolarization relies on the complex interplay between a provocative arrhythmic trigger and vulnerable arrhythmic substrate, with a central role played by the excessive prolongation of ventricular action potential duration, impaired intracellular Ca handling, and slowed impulse conduction. This review outlines the electrical activity of ventricular myocytes in normal conditions and cardiac disease, describes classical electrophysiological mechanisms of cardiac arrhythmia, and provides an update on repolarization-related surrogates currently used to assess arrhythmic propensity, including spatial dispersion of repolarization, activation-repolarization coupling, electrical restitution, TRIaD (triangulation, reverse use dependence, instability, and dispersion), and the electromechanical window. This is followed by a discussion of the mechanisms that account for the dependence of arrhythmic vulnerability on the location of the ventricular pacing site. Finally, the review clarifies the electrophysiological basis for cardiac arrhythmia produced by hypokalaemia, and gives insight into the clinical importance and pathophysiology of drug-induced arrhythmia, with particular focus on class Ia (quinidine, procainamide) and Ic (flecainide) Na channel blockers, and class III antiarrhythmic agents that block the delayed rectifier K channel (dofetilide).

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Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 85%

Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 99%

Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 99%

Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 99%

Section: Impact Of Ventricular Pacing Site On Arrhythmic Vulnerabilitymentioning

confidence: 99%

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Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Osadchii

2017

Acta Physiologica

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Impaired epicardial activation–repolarization coupling contributes to the proarrhythmic effects of hypokalaemia and dofetilide in guinea pig ventricles

Osadchii

2014

Acta Physiologica

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Arrhythmic substrate, slowed propagation and increased dispersion in conduction direction in the right ventricular outflow tract of murine Scn5a+/− hearts

et al. 2014

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AimTo test a hypothesis attributing arrhythmia in Brugada Syndrome to right ventricular (RV) outflow tract (RVOT) conduction abnormalities arising from Nav1.5 insufficiency and fibrotic change.MethodsArrhythmic properties of Langendorff-perfused Scn5a+/− and wild-type mouse hearts were correlated with ventricular effective refractory periods (VERPs), multi-electrode array (MEA) measurements of action potential (AP) conduction velocities and dispersions in conduction direction (CD), Nav1.5 expression levels, and fibrotic change, as measured at the RVOT and RV. Two-way anova was used to test for both independent and interacting effects of anatomical region and genotype on these parameters.ResultsScn5a+/− hearts showed greater arrhythmic frequencies during programmed electrical stimulation at the RVOT but not the RV. The Scn5a+/− genotype caused an independent increase of VERP regardless of whether the recording site was the RVOT or RV. Effective AP conduction velocities (CV†s), derived from fitting regression planes to arrays of observed local activation times were reduced in Scn5a+/− hearts and at the RVOT independently. AP conduction velocity magnitudes derived by averaging MEA results from local vector analyses, CV*, were reduced by the Scn5a+/− genotype alone. In contrast, dispersions in conduction direction, were greater in the RVOT than the RV, when the atrioventricular node was used as the pacing site. The observed reductions in Nav1.5 expression were attributable to Scn5a+/−, whereas increased levels of fibrosis were associated with the RVOT.ConclusionsThe Scn5a+/− RVOT recapitulates clinical findings of increased arrhythmogenicity through reduced CV† reflecting reduced CV* attributable to reduced Nav1.5 expression and increased CD attributable to fibrosis.

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Electrophysiological determinants of arrhythmic susceptibility upon endocardial and epicardial pacing in guinea‐pig heart

Cited by 6 publications

References 38 publications

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

Impaired epicardial activation–repolarization coupling contributes to the proarrhythmic effects of hypokalaemia and dofetilide in guinea pig ventricles

Arrhythmic substrate, slowed propagation and increased dispersion in conduction direction in the right ventricular outflow tract of murine Scn5a+/− hearts

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