Proarrhythmia

Roden, Dan M.; Anderson, Mark E.

doi:10.1007/3-540-29715-4_3

Cited by 32 publications

(30 citation statements)

References 94 publications

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“…These results suggest that acacetin may have the potential to cause QT prolongation. 7 However, acacetin (30 mol/L), in contrast to quinidine (10 mol/L), did not affect heart rate and did not cause QTc prolongation in isolated hypokalemic rabbit hearts (Figure 7). Blockade of the ultrarapid delayed rectifier current I Kur (or Kv1.5) channel has been proposed as a novel target for the development of safer and potentially more effective atrial antiarrhythmic agents.…”

Section: Discussionmentioning

confidence: 93%

Acacetin, a Natural Flavone, Selectively Inhibits Human Atrial Repolarization Potassium Currents and Prevents Atrial Fibrillation in Dogs

et al. 2008

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Background-The development of atrium-selective antiarrhythmic agents is a current strategy for inhibiting atrial fibrillation (AF). The present study investigated whether the natural flavone acacetin from the traditional Chinese medicine Xuelianhua would be an atrium-selective anti-AF agent. Methods and Results-The effects of acacetin on human atrial ultrarapid delayed rectifier K ϩ current (I Kur ) and other cardiac ionic currents were studied with a whole-cell patch technique. Acacetin suppressed I Kur and the transient outward K ϩ current (IC 50 3.2 and 9.2 mol/L, respectively) and prolonged action potential duration in human atrial myocytes. The compound blocked the acetylcholine-activated K ϩ current; however, it had no effect on the Na ϩ current, L-type Ca 2ϩ current, or inward-rectifier K ϩ current in guinea pig cardiac myocytes. Although acacetin caused a weak reduction in the hERG and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells, it did not prolong the corrected QT interval in rabbit hearts. In anesthetized dogs, acacetin (5 mg/kg) prolonged the atrial effective refractory period in both the right and left atria 1 to 4 hours after intraduodenal administration without prolongation of the corrected QT interval, whereas sotalol at 5 mg/kg prolonged both the atrial effective refractory period and the corrected QT interval. Acacetin prevented AF induction at doses of 2.5 mg/kg (50%), 5 mg/kg (85.7%), and 10 mg/kg (85.7%). Sotalol 5 mg/kg also prevented AF induction (60%). Conclusions-The present study demonstrates that the natural compound acacetin is an atrium-selective agent that prolongs the atrial effective refractory period without prolonging the corrected QT interval and effectively prevents AF in anesthetized dogs after intraduodenal administration. These results indicate that oral acacetin is a promising atrium-selective agent for the treatment of AF.

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Section: Discussionmentioning

confidence: 93%

Acacetin, a Natural Flavone, Selectively Inhibits Human Atrial Repolarization Potassium Currents and Prevents Atrial Fibrillation in Dogs

et al. 2008

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“…4,14 However, quinidine itself is a cause of TdP and arrhythmic sudden death. The mechanism of quinidine-induced TdP has been attributed to QT prolongation due to inhibition of I Kr 15,16. The present study examines the critical role of late I Na in modulating the arrhythmogenicity of quinidine.…”

Section: Discussionmentioning

confidence: 93%

Role of late sodium current in modulating the proarrhythmic and antiarrhythmic effects of quinidine

Guo

et al. 2008

Heart Rhythm

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“…In susceptible patients, antiarrhythmic drugs at therapeutic concentrations may paradoxically aggravate existing cardiac electrical instability or even provoke new symptomatic arrhythmia . The arrhythmogenic responses range from an increased number of ectopic beats, which is rarely perceived by the patient, to malignant VT that can lead to sudden death.…”

Section: Arrhythmogenic Responses To Antiarrhythmic Drugsmentioning

confidence: 99%

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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Proarrhythmia

Cited by 32 publications

References 94 publications

Acacetin, a Natural Flavone, Selectively Inhibits Human Atrial Repolarization Potassium Currents and Prevents Atrial Fibrillation in Dogs

Acacetin, a Natural Flavone, Selectively Inhibits Human Atrial Repolarization Potassium Currents and Prevents Atrial Fibrillation in Dogs

Role of late sodium current in modulating the proarrhythmic and antiarrhythmic effects of quinidine

Role of abnormal repolarization in the mechanism of cardiac arrhythmia

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