Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/30169
Title: Pulmonary delivery of flecainide causes a rate-dependent predominant effect on atrial compared with ventricular depolarization duration revealed by intracardiac recordings in an intact porcine model
Authors: ANTONIO, Victor Z. deSILVA, Anderson C.STOCCO, Fernando G.SILVA, Bruna A.MARUM, Alexandre A.BORTOLOTTO, Alexandre L.BELARDINELLI, LuizVERRIER, Richard L.
Citation: JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, v.29, n.11, p.1563-1569, 2018
Abstract: Background Pulmonary delivery of flecainide results in the rapid conversion of atrial fibrillation (AF) to normal sinus rhythm in large-animal models and is safe and well-tolerated by normal human volunteers. Objective Methods We investigated the effects of pulmonary delivery of flecainide on atrial and ventricular depolarization and repolarization duration. Intratracheal instillation (1.5 mg/kg, rapid push) of flecainide or sterile water (placebo) was performed in 12 closed-chest, anesthetized Yorkshire pigs with a catheter positioned at the bifurcation of the main bronchi. High-resolution electrograms obtained from catheters fluoroscopically positioned in the right atrium and left ventricle circumvented measurement errors due to the fusion of P and T waves in surface leads when rapid heart rates shortened the TP interval. Pacing was achieved using electrical stimuli delivered via right atrial catheter electrodes. Results Conclusion During sinus rhythm (98 +/- 4.7 beats/min), intratracheal flecainide caused comparable (P = 0.56) increases in atrial depolarization (P-a) duration by 22% (39.8 +/- 3.2 to 48.7 +/- 3.3 milliseconds) and left ventricular (LV) QRS complex duration by 20% (47.9 +/- 1.6 to 57.3 +/- 1.8 milliseconds) at peak effect at 2 minutes post-dosing. During right atrial pacing at 180 beats/min, P-a duration increased by 55% (37.0 +/- 2.0 to 57.2 +/- 1.6 milliseconds; P < 0.0001). The atrial response was greater (p = 0.001) than the 30% increase in LV QRS complex duration (46.6 +/- 1.7 to 60.6 +/- 2.5 milliseconds; P = 0.005). P-a duration and QRS complex duration were unchanged by placebo independent of pacing (P >= 0.4 for both). Atrial repolarization duration (PTa; P = 0.46) and QT(c) interval (P = 0.49) remained unchanged. Intratracheal flecainide exerts a rate-dependent, predominant effect on atrial compared with ventricular depolarization duration. Pulmonary delivery of flecainide could facilitate AF conversion to sinus rhythm with reduced ventricular proarrhythmia risk.
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