Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPVERRIER, Richard L.BORTOLOTTO, Alexandre L.SILVA, Bruna A.MARUM, Alexandre A.STOCCO, Fernando G.EVARISTO, EdersonANTONIO, Victor Z. deSILVA, Anderson C.BELARDINELLI, Luiz2019-01-172019-01-172018HEART RHYTHM, v.15, n.12, p.1882-1888, 20181547-5271https://observatorio.fm.usp.br/handle/OPI/30152BACKGROUND 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.engrestrictedAccessAtrial fibrillationAtrial depolarization durationFlecainideIntratracheal instillationPulmonary deliverysodium-channel blockantiarrhythmic-drug therapyranolazinemanagementstrategypotentarticleCopyright ELSEVIER SCIENCE INC10.1016/j.hrthm.2018.06.036Cardiac & Cardiovascular Systems1556-3871