“Early” Class III Drugs for the Treatment of Atrial Fibrillation

Blaauw, Yuri; Gögelein, Heinz; Tieleman, RG; Hunnik, Arne van; Schotten, Ulrich; Allessie, Maurits A.

doi:10.1161/01.cir.0000143050.22291.2e

Cited by 166 publications

(52 citation statements)

References 24 publications

(15 reference statements)

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“…642,644,645,647 AVE0118 is an I Kur and I to blocker that, unlike dofetilide, increases refractoriness in electrically remodeled atria, prolongs atrial wavelength, and converts persistent AF to sinus rhythm without disturbing intra-atrial conduction velocity or prolonging the QT interval. 648 …”

Section: Atrioselective Agentsmentioning

confidence: 99%

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation

Fuster¹,

Rydén²,

Cannom³

et al. 2006

Circulation

1,877

589

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Section: Atrioselective Agentsmentioning

confidence: 99%

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation

Fuster¹,

Rydén²,

Cannom³

et al. 2006

Circulation

1,877

589

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“…17 The rotor was terminated when producing selective blockade (90%) of I Kur or I to , but not the fast or slow delayed rectifier K + currents (I Kr and I Ks ). 16 Remarkably, prolongation of the APD at the plateau led to tip meander and eventual wavebreak and rotor termination.…”

Section: Ionic Current Modifications and A Trial Fibrillationmentioning

confidence: 99%

Cardiac fibrillation: From ion channels to rotors in the human heart

Vaquero¹,

Calvo²,

Jalife³

2008

Heart Rhythm

158

134

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Cardiac fibrillation is one of the most important causes of morbidity and mortality in the developed world, but its mechanisms are still a matter of debate. Not only is the role of certain ion channels currently being unraveled, but also investigators are starting to gather evidence for the dynamics and molecular mechanisms of both atrial (AF) and ventricular (VF) fibrillation in humans. In this brief review, we evaluate the available evidence for the separate roles played by individual sarcolemmal ion channels in AF and VF, assessing the clinical relevance of such findings. Importantly, while human data support the idea that rotors are a crucial mechanism for fibrillation maintenance in both the atria and the ventricles, there are clear inherent differences between the two chamber types, particularly in regards to the role of specific ion channels in fibrillation. But there are also similarities. This knowledge, together with new information on the changes that take place during disease evolution and between structurally normal and diseased hearts may enhance our understanding of fibrillatory processes pointing to new pharmacological or interventionist approaches to improve disease outcomes.

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“…I Kur block selectively prolongs atrial repolarization and can suppress AF. 9,11 Hence, pharmaceutical investigations have focused on developing selective inhibitors of the human atrial I Kur or hKv1.5 channels 12 ; however, no such therapeutic agent is commercially available. Traditional Chinese medicine may be a great resource that can be used to develop this type of drug.…”

Section: Clinical Perspective P 2457mentioning

confidence: 99%

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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“Early” Class III Drugs for the Treatment of Atrial Fibrillation

Cited by 166 publications

References 24 publications

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation

Cardiac fibrillation: From ion channels to rotors in the human heart

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

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