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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.identifier.citationHEART RHYTHM, v.15, n.12, p.1882-1888, 2018
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.sponsorshipInCarda Therapeutics, Inc.
dc.relation.ispartofHeart Rhythm
dc.subjectAtrial fibrillationeng
dc.subjectAtrial depolarization durationeng
dc.subjectIntratracheal instillationeng
dc.subjectPulmonary deliveryeng
dc.subject.othersodium-channel blockeng
dc.subject.otherantiarrhythmic-drug therapyeng
dc.titleAccelerated conversion of atrial fibrillation to normal sinus rhythm by pulmonary delivery of flecainide acetate in a porcine modeleng
dc.rights.holderCopyright ELSEVIER SCIENCE INCeng
dc.subject.wosCardiac & Cardiovascular Systemseng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng, Richard L.:Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA; Harvard Med Sch, Boston, MA 02215 USA, Luiz:InCarda Therapeut Inc, Newark, CA USA
hcfmusp.publisher.cityNEW YORKeng
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