Article: Acacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs

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TitleAcacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs
AuthorsLi, GR1 3
Wang, HB2
Qin, GW2
Jin, MW4
Tang, Q4
Sun, HY1
Du, XL1
Deng, XL1
Zhang, XH4
Chen, JB4
Chen, L4
Xu, XH4
Cheng, LC3
Chiu, SW3
Tse, HF1
Vanhoutte, PM1
Lau, CP1
KeywordsArrhythmia
Drugs
Electrophysiology
Ion channels
Pharmacology
Issue Date2008
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.org
CitationCirculation, 2008, v. 117 n. 19, p. 2449-2457 [How to Cite?]
DOI: http://dx.doi.org/10.1161/CIRCULATIONAHA.108.769554
AbstractBACKGROUND - 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 current (IKur) and other cardiac ionic currents were studied with a whole-cell patch technique. Acacetin suppressed IKur and the transient outward K current (IC50 3.2 and 9.2 μmol/L, respectively) and prolonged action potential duration in human atrial myocytes. The compound blocked the acetylcholine- activated K current; however, it had no effect on the Na current, L-type Ca current, or inward-rectifier K 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. © 2008 American Heart Association, Inc.
ISSN0009-7322
2011 Impact Factor: 14.739
2011 SCImago Journal Rankings: 1.390
DOIhttp://dx.doi.org/10.1161/CIRCULATIONAHA.108.769554
ISI Accession Number IDWOS:000255776700005
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLi, GR
dc.contributor.authorWang, HB
dc.contributor.authorQin, GW
dc.contributor.authorJin, MW
dc.contributor.authorTang, Q
dc.contributor.authorSun, HY
dc.contributor.authorDu, XL
dc.contributor.authorDeng, XL
dc.contributor.authorZhang, XH
dc.contributor.authorChen, JB
dc.contributor.authorChen, L
dc.contributor.authorXu, XH
dc.contributor.authorCheng, LC
dc.contributor.authorChiu, SW
dc.contributor.authorTse, HF
dc.contributor.authorVanhoutte, PM
dc.contributor.authorLau, CP
dc.date.accessioned2010-09-06T07:27:19Z
dc.date.available2010-09-06T07:27:19Z
dc.date.issued2008
dc.description.abstractBACKGROUND - 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 current (IKur) and other cardiac ionic currents were studied with a whole-cell patch technique. Acacetin suppressed IKur and the transient outward K current (IC50 3.2 and 9.2 μmol/L, respectively) and prolonged action potential duration in human atrial myocytes. The compound blocked the acetylcholine- activated K current; however, it had no effect on the Na current, L-type Ca current, or inward-rectifier K 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. © 2008 American Heart Association, Inc.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationCirculation, 2008, v. 117 n. 19, p. 2449-2457 [How to Cite?]
DOI: http://dx.doi.org/10.1161/CIRCULATIONAHA.108.769554
dc.identifier.doihttp://dx.doi.org/10.1161/CIRCULATIONAHA.108.769554
dc.identifier.epage2457
dc.identifier.hkuros146209
dc.identifier.isiWOS:000255776700005
dc.identifier.issn0009-7322
2011 Impact Factor: 14.739
2011 SCImago Journal Rankings: 1.390
dc.identifier.issue19
dc.identifier.openurl
dc.identifier.pmid18458165
dc.identifier.scopuseid_2-s2.0-43449090419
dc.identifier.spage2449
dc.identifier.urihttp://hdl.handle.net/10722/77012
dc.identifier.volume117
dc.languageeng
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circ.ahajournals.org
dc.publisher.placeUnited States
dc.relation.ispartofCirculation
dc.relation.referencesReferences in Scopus
dc.rightsCirculation. Copyright © Lippincott Williams & Wilkins.
dc.subject.meshAction Potentials - drug effects
dc.subject.meshAnimals
dc.subject.meshAnti-Arrhythmia Agents - pharmacology
dc.subject.meshAtrial Fibrillation - drug therapy - prevention & control
dc.subject.meshAtrial Function - drug effects
dc.subject.meshCells, Cultured
dc.subject.meshFlavones - pharmacology - therapeutic use
dc.subject.meshGuinea Pigs
dc.subject.meshHumans
dc.subject.meshMedicine, Chinese Traditional
dc.subject.meshMyocytes, Cardiac
dc.subject.meshPatch-Clamp Techniques
dc.subject.meshPotassium - metabolism
dc.subjectArrhythmia
dc.subjectDrugs
dc.subjectElectrophysiology
dc.subjectIon channels
dc.subjectPharmacology
dc.titleAcacetin, a natural flavone, selectively inhibits human atrial repolarization potassium currents and prevents atrial fibrillation in dogs
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences
  3. The University of Hong Kong
  4. Huazhong University of Science and Technology