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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
2013 Impact Factor: 14.948
 
DOIhttp://dx.doi.org/10.1161/CIRCULATIONAHA.108.769554
 
ISI Accession Number IDWOS:000255776700005
 
ReferencesReferences in Scopus
 
DC FieldValue
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.eissn1524-4539
 
dc.identifier.epage2457
 
dc.identifier.f10001120731
 
dc.identifier.f10001120731
 
dc.identifier.f10001120731
 
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dc.identifier.f10001120731
 
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dc.identifier.hkuros146209
 
dc.identifier.isiWOS:000255776700005
 
dc.identifier.issn0009-7322
2013 Impact Factor: 14.948
 
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
 
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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