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Article: Electrophysiologic effects of chronic amiodarone therapy and hypothyroidism, alone and in combination, on guinea pig ventricular myocytes

TitleElectrophysiologic effects of chronic amiodarone therapy and hypothyroidism, alone and in combination, on guinea pig ventricular myocytes
Authors
Issue Date1999
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
Citation
Journal Of Pharmacology And Experimental Therapeutics, 1999, v. 289 n. 1, p. 156-165 How to Cite?
AbstractAmiodarone is a widely used antiarrhythmic drug, the mechanisms of action of which remain incompletely understood. Indirect evidence suggests that the class III properties of amiodarone may be mediated by cardiac antithyroid effects. We sought to determine whether the effects of chronic amiodarone on repolarization in guinea pig hearts can be attributed to an antithyroid action by studying the changes in dofetilide-sensitive rapid (I(Kr)) and dofetilide-resistant slow (I(Ks)) delayed rectifier currents, inward rectifier K+ current (I(K1)), and action potentials of ventricular myocytes from five groups of guinea pigs: control, hypothyroid, amiodarone- treated for 7 days, hypothyroid plus amiodarone, and vehicle (dimethyl sulfoxide) treated. I(Ks) was reduced by amiodarone (to 61% of control, P < .05, at 50 mV) but was more strongly reduced by hypothyroidism (to 35% of control, P < .01, 50 mV). Amiodarone significantly reduced I(Kr) and I(K1) (by 55 and 64% at 10 mV and -50 mV, respectively), which were unaffected by hypothyroidism. Amiodarone alone and hypothyroidism alone had similar action potential-prolonging actions. Hypothyroid animals treated with amiodarone showed a combination of ionic effects (strong I(Ks) reduction, similar to hypothyroidism alone; reduced I(Kr) and I(K1), similar to amiodarone alone), along with action potential prolongation significantly greater than that caused by either intervention alone. We conclude that chronic amiodarone and hypothyroidism have different effects on ionic currents and that their combination prolongs action potential duration to a greater extent than either alone in guinea pig hearts, suggesting that the class III actions of amiodarone are not mediated by a cardiac hypothyroid state.
Persistent Identifierhttp://hdl.handle.net/10722/162311
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBosch, RFen_US
dc.contributor.authorLi, GRen_US
dc.contributor.authorGaspo, Ren_US
dc.contributor.authorNattel, Sen_US
dc.date.accessioned2012-09-05T05:18:52Z-
dc.date.available2012-09-05T05:18:52Z-
dc.date.issued1999en_US
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 1999, v. 289 n. 1, p. 156-165en_US
dc.identifier.issn0022-3565en_US
dc.identifier.urihttp://hdl.handle.net/10722/162311-
dc.description.abstractAmiodarone is a widely used antiarrhythmic drug, the mechanisms of action of which remain incompletely understood. Indirect evidence suggests that the class III properties of amiodarone may be mediated by cardiac antithyroid effects. We sought to determine whether the effects of chronic amiodarone on repolarization in guinea pig hearts can be attributed to an antithyroid action by studying the changes in dofetilide-sensitive rapid (I(Kr)) and dofetilide-resistant slow (I(Ks)) delayed rectifier currents, inward rectifier K+ current (I(K1)), and action potentials of ventricular myocytes from five groups of guinea pigs: control, hypothyroid, amiodarone- treated for 7 days, hypothyroid plus amiodarone, and vehicle (dimethyl sulfoxide) treated. I(Ks) was reduced by amiodarone (to 61% of control, P < .05, at 50 mV) but was more strongly reduced by hypothyroidism (to 35% of control, P < .01, 50 mV). Amiodarone significantly reduced I(Kr) and I(K1) (by 55 and 64% at 10 mV and -50 mV, respectively), which were unaffected by hypothyroidism. Amiodarone alone and hypothyroidism alone had similar action potential-prolonging actions. Hypothyroid animals treated with amiodarone showed a combination of ionic effects (strong I(Ks) reduction, similar to hypothyroidism alone; reduced I(Kr) and I(K1), similar to amiodarone alone), along with action potential prolongation significantly greater than that caused by either intervention alone. We conclude that chronic amiodarone and hypothyroidism have different effects on ionic currents and that their combination prolongs action potential duration to a greater extent than either alone in guinea pig hearts, suggesting that the class III actions of amiodarone are not mediated by a cardiac hypothyroid state.en_US
dc.languageengen_US
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.orgen_US
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeuticsen_US
dc.subject.meshAction Potentials - Drug Effectsen_US
dc.subject.meshAmiodarone - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnti-Arrhythmia Agents - Pharmacologyen_US
dc.subject.meshCell Separationen_US
dc.subject.meshDelayed Rectifier Potassium Channelsen_US
dc.subject.meshElectrocardiography - Drug Effectsen_US
dc.subject.meshElectrophysiologyen_US
dc.subject.meshGuinea Pigsen_US
dc.subject.meshHeart Rate - Drug Effectsen_US
dc.subject.meshHeart Ventricles - Drug Effects - Pathologyen_US
dc.subject.meshHypothyroidism - Pathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMyocardium - Pathologyen_US
dc.subject.meshPatch-Clamp Techniquesen_US
dc.subject.meshPotassium Channels - Drug Effectsen_US
dc.subject.meshPotassium Channels, Inwardly Rectifyingen_US
dc.subject.meshPotassium Channels, Voltage-Gateden_US
dc.titleElectrophysiologic effects of chronic amiodarone therapy and hypothyroidism, alone and in combination, on guinea pig ventricular myocytesen_US
dc.typeArticleen_US
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_US
dc.identifier.authorityLi, GR=rp00476en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid10086999-
dc.identifier.scopuseid_2-s2.0-0032893049en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032893049&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume289en_US
dc.identifier.issue1en_US
dc.identifier.spage156en_US
dc.identifier.epage165en_US
dc.identifier.isiWOS:000079365700020-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridBosch, RF=7102263519en_US
dc.identifier.scopusauthoridLi, GR=7408462932en_US
dc.identifier.scopusauthoridGaspo, R=6603283635en_US
dc.identifier.scopusauthoridNattel, S=36048738800en_US

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