Accelerated conversion of atrial fibrillation to normal sinus rhythm by pulmonary delivery of flecainide acetate in a porcine model

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorVERRIER, Richard L.
dc.contributor.authorBORTOLOTTO, Alexandre L.
dc.contributor.authorSILVA, Bruna A.
dc.contributor.authorMARUM, Alexandre A.
dc.contributor.authorSTOCCO, Fernando G.
dc.contributor.authorEVARISTO, Ederson
dc.contributor.authorANTONIO, Victor Z. de
dc.contributor.authorSILVA, Anderson C.
dc.contributor.authorBELARDINELLI, Luiz
dc.date.accessioned2019-01-17T13:39:08Z
dc.date.available2019-01-17T13:39:08Z
dc.date.issued2018
dc.description.abstractBACKGROUND Pulmonary delivery of antiarrhythmic agents has the potential to increase rapidly targeted drug concentrations in pulmonary veins and left atrium to terminate atrial fibrillation (AF). OBJECTIVE We evaluated the efficacy of flecainide administered via intratracheal instillation in terminating AF in a reliable preclinical model. METHODS In 11 closed-chest anesthetized Yorkshire pigs, AF was induced by intrapericardial administration of acetylcholine (1 mL of 102.5 mM solution) followed by burst pacing and allowed to continue for 2 minutes before intratracheal flecainide (0.4 or 0.75 mg/kg) administration. RESULTS Both the 0.4-and 0.75-mg/kg doses of intratracheal flecainide significantly reduced AF duration by 35% (P = .02) and 54% (P = .001), respectively, compared to no-drug baseline. There was a strong inverse correlation (r(2) = 0.87; P = .03) between the duration of AF and the change in atrial depolarization duration in response to intratracheal flecainide. Induction of AF resulted in a marked increase in ventricular rate and corresponding reduction in mean arterial pressure, which returned to baseline levels within 5 minutes after conversion. CONCLUSION Intratracheal flecainide instillation is effective in rapidly converting AF to normal sinus rhythm and restoring mean arterial pressure and heart rate to baseline values. The basis for this efficacy is likely rapid absorption of the drug through the lungs and delivery as a first-pass bolus to the left atrial and ventricular chambers and then to the coronary arterial circulation. The antiAF effect of flecainide is inversely correlated with the drug's prolongation of atrial depolarization, implicating slowing of intra-atrial conduction as an important mechanism underlying conversion of AF to normal sinus rhythm.eng
dc.description.indexMEDLINEeng
dc.description.sponsorshipInCarda Therapeutics, Inc.
dc.identifier.citationHEART RHYTHM, v.15, n.12, p.1882-1888, 2018
dc.identifier.doi10.1016/j.hrthm.2018.06.036
dc.identifier.eissn1556-3871
dc.identifier.issn1547-5271
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/30152
dc.language.isoeng
dc.publisherELSEVIER SCIENCE INCeng
dc.relation.ispartofHeart Rhythm
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright ELSEVIER SCIENCE INCeng
dc.subjectAtrial fibrillationeng
dc.subjectAtrial depolarization durationeng
dc.subjectFlecainideeng
dc.subjectIntratracheal instillationeng
dc.subjectPulmonary deliveryeng
dc.subject.othersodium-channel blockeng
dc.subject.otherantiarrhythmic-drug therapyeng
dc.subject.otherranolazineeng
dc.subject.othermanagementeng
dc.subject.otherstrategyeng
dc.subject.otherpotenteng
dc.subject.wosCardiac & Cardiovascular Systemseng
dc.titleAccelerated conversion of atrial fibrillation to normal sinus rhythm by pulmonary delivery of flecainide acetate in a porcine modeleng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalVERRIER, Richard L.:Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA; Harvard Med Sch, Boston, MA 02215 USA
hcfmusp.author.externalBELARDINELLI, Luiz:InCarda Therapeut Inc, Newark, CA USA
hcfmusp.citation.scopus13
hcfmusp.contributor.author-fmusphcALEXANDRE LEMOS BORTOLOTTO
hcfmusp.contributor.author-fmusphcBRUNA ARAUJO SILVA
hcfmusp.contributor.author-fmusphcALEXANDRE AMATRUDA MARUM
hcfmusp.contributor.author-fmusphcFERNANDO GALASSI STOCCO NETO
hcfmusp.contributor.author-fmusphcEDERSON EVARISTO
hcfmusp.contributor.author-fmusphcVICTOR ZANDONA DE ANTONIO
hcfmusp.contributor.author-fmusphcANDERSON CARVALHO DA SILVA
hcfmusp.description.beginpage1882
hcfmusp.description.endpage1888
hcfmusp.description.issue12
hcfmusp.description.volume15
hcfmusp.origemWOS
hcfmusp.origem.pubmed29958990
hcfmusp.origem.scopus2-s2.0-85051046946
hcfmusp.origem.wosWOS:000451448600028
hcfmusp.publisher.cityNEW YORKeng
hcfmusp.publisher.countryUSAeng
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hcfmusp.scopus.lastupdate2024-05-17
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