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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.
Journal of Cardiovascular Electrophysiology 2018 August 15
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: We investigated the effects of pulmonary delivery of flecainide on atrial and ventricular depolarization and repolarization duration.
METHODS: 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: 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, Pa 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). Pa 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 QTc interval (P = 0.49) remained unchanged.
CONCLUSION: 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.
OBJECTIVE: We investigated the effects of pulmonary delivery of flecainide on atrial and ventricular depolarization and repolarization duration.
METHODS: 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: 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, Pa 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). Pa 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 QTc interval (P = 0.49) remained unchanged.
CONCLUSION: 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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