Different effects of amiodarone and dofetilide on the dispersion of repolarization between well-coupled ventricular and Purkinje fibers1

Increased transmural dispersion of repolarization is an established contributing factor to ventricular tachyarrhythmias. In this study, we evaluated the effect of chronic amiodarone treatment and acute administration of dofetilide in canine cardiac preparations containing electrotonically coupled Purkinje fibers (PFs) and ventricular muscle (VM) and compared the effects to those in uncoupled PF and VM preparations using the conventional microelectrode technique. Dispersion between PFs and VM was inferred from the difference in the respective action potential durations (APDs). In coupled preparations, amiodarone decreased the difference in APDs between PFs and VM, thus decreasing dispersion. In the same preparations, dofetilide increased the dispersion by causing a more pronounced prolongation in PFs. This prolongation was even more emphasized in uncoupled PF preparations, while the effect in VM was the same. In uncoupled preparations, amiodarone elicited no change on the difference in APDs. In conclusion, amiodarone decreased the dispersion between PFs and VM, while dofetilide increased it. The measured difference in APD between cardiac regions may be the affected by electrotonic coupling; thus, studying PFs and VM separately may lead to an over- or underestimation of dispersion.

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Transmural dispersion of repolarization and ventricular tachyarrhythmias

Journal of Electrocardiology ◽

10.1016/j.jelectrocard.2004.02.002 ◽

2004 ◽

Vol 37 (3) ◽

pp. 191-200 ◽

Cited By ~ 110

Author(s):

Norikazu Watanabe ◽

Youichi Kobayashi ◽

Kaoru Tanno ◽

Fumito Miyoshi ◽

Taku Asano ◽

...

Keyword(s):

Ventricular Tachyarrhythmias ◽

Dispersion Of Repolarization ◽

Transmural Dispersion Of Repolarization ◽

Transmural Dispersion

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Transmural Dispersion of Repolarization Determines Scroll Wave Behavior During Ventricular Tachyarrhythmias

Circulation Journal ◽

10.1253/circj.cj-10-0071 ◽

2011 ◽

Vol 75 (1) ◽

pp. 80-88 ◽

Cited By ~ 7

Author(s):

Ryo Haraguchi ◽

Takashi Ashihara ◽

Tsunetoyo Namba ◽

Kunichika Tsumoto ◽

Shingo Murakami ◽

...

Keyword(s):

Ventricular Tachyarrhythmias ◽

Dispersion Of Repolarization ◽

Transmural Dispersion Of Repolarization ◽

Scroll Wave ◽

Transmural Dispersion

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211 Validation of transmural dispersion of repolarization in a large series of Brugada syndrome patients. Increased Tpeak-Tend interval in Brugada syndrome is independantly related to symptoms or arrhythm

Archives of Cardiovascular Diseases Supplements ◽

10.1016/s1878-6480(12)70607-9 ◽

2012 ◽

Vol 4 (1) ◽

pp. 67

Author(s):

Anne Rollin ◽

Philippe Maury ◽

Frederic Sacher ◽

Jean Luc Pasquié ◽

Frank Raczka ◽

...

Keyword(s):

Brugada Syndrome ◽

Large Series ◽

Dispersion Of Repolarization ◽

Transmural Dispersion Of Repolarization ◽

Transmural Dispersion

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Reduction of repolarization reserve unmasks the proarrhythmic role of endogenous late Na+ current in the heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00467.2009 ◽

2009 ◽

Vol 297 (3) ◽

pp. H1048-H1057 ◽

Cited By ~ 42

Author(s):

Lin Wu ◽

Sridharan Rajamani ◽

Hong Li ◽

Craig T. January ◽

John C. Shryock ◽

...

Keyword(s):

Torsade De Pointes ◽

Polymorphic Ventricular Tachycardia ◽

Isolated Hearts ◽

T Wave ◽

Dispersion Of Repolarization ◽

Transmural Dispersion Of Repolarization ◽

Repolarization Reserve ◽

Monophasic Action Potentials ◽

Transmural Dispersion

Reduction of repolarization reserve increases the risk of arrhythmia. We hypothesized that inhibition of K+ current ( IK) to decrease repolarization reserve would unmask the proarrhythmic role of endogenous, physiological late Na+ current (late INa). Monophasic action potentials (MAP) and 12-lead electrocardiogram were recorded from female rabbit isolated hearts. To block IK and reduce repolarization reserve, E-4031, 4-aminopyridine, and BaCl2 were used; to block endogenous late INa, tetrodotoxin (TTX) and ranolazine were used. E-4031 (1–60 nM) concentration-dependently prolonged MAP duration (MAPD90) and increased duration of the T wave from Tpeak to Tend (Tpeak-Tend), transmural dispersion of repolarization (TDR), and beat-to-beat variability (BVR) of MAPD90. E-4031 caused spontaneous and pause-triggered polymorphic ventricular tachycardia [ torsade de pointes (TdP)]. In the presence of 60 nM E-4031, TTX (0.6–3 μM) and ranolazine (5–10 μM) shortened MAPD90, decreased TDR, BVR, and Tpeak-Tend ( n = 9–20, P < 0.01), and abolished episodes of TdP. In hearts treated with BaCl2 or 4-aminopyridine plus E-4031, TTX (0.6–3 μM) shortened MAPD90 and decreased Tpeak-Tend. Ranolazine could not reverse the effect of E-4031 to inhibit human ether-a-go-go-related gene (HERG) K+ current; thus, the reversal by ranolazine of effects of E-4031 was likely due to inhibition of late INa and not to antagonism of the HERG-blocking action of E-4031. We conclude that endogenous, physiological late INa contributes to arrhythmogenesis in hearts with reduced repolarization reserve. Inhibition of this current partially reverses MAPD prolongation and abolishes arrhythmic activity caused by IK inhibitors.

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Abstract 1872: Transmural Dispersion of Repolarization in Human Ventricular Wall

Circulation ◽

10.1161/circ.118.suppl_18.s_397-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Alexey V Glukhov ◽

Vadim V Fedorov ◽

Kelley V Foyil ◽

Nader Moazami ◽

Igor R Efimov

Keyword(s):

Animal Models ◽

M Cells ◽

Ventricular Wall ◽

Cmos Camera ◽

Distinct Population ◽

Dispersion Of Repolarization ◽

Transmural Dispersion Of Repolarization ◽

Transmural Dispersion ◽

First Time ◽

Long Action

Transmural dispersion of repolartization (DR) has been studied in numerous animal models. Some studies presented evidence of midmyocardial population of M-cells that possess distinctly long action potential duration (APD). We aimed to investigate APD and DR in explanted failing human left ventricles (LV). We optically mapped APD in coronary-perfused human LV wedge preparations (n=4) using CMOS camera in presence of blebbistatin (BB, 10 μ M). Microelectrode recordings were used to validate BB in human LV. RESULTS: During slow pacing (S1S1=2,000ms), APD at the endo-, mid-, and epicardium was 586±27ms, 578±19ms, and 496±14ms, respectively. Maximum APD gradient was 24±5 ms/mm, DR was 35±6 ms. Progressive decrease in S1S1 up to functional refractory period (460±26 ms) induced an inhomogeneous shortening of APD (up to 350±26 ms, 352±36 ms and 346±30 ms, respectively), decrease in APD gradient and DR (4±3 ms/mm and 20±4 ms, respectively, p<0.01) We present for the first time evidence of transmural APD gradient in failing human LV. However, we could not confirm presence of distinct population of M-cells that were found in several animal models.

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