Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Department of Environmental Sciences, Harvard School of Public Health, Boston, Massachusetts.
J Cardiovasc Electrophysiol. 2018 Nov;29(11):1563-1569. doi: 10.1111/jce.13708. Epub 2018 Sep 14.
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.
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.
During sinus rhythm (98 ± 4.7 beats/min), intratracheal flecainide caused comparable (P = 0.56) increases in atrial depolarization (P ) 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 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 duration and QRS complex duration were unchanged by placebo independent of pacing (P ≥ 0.4 for both). Atrial repolarization duration (PT ; P = 0.46) and QT 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.
氟卡尼经肺部给药可使大型动物模型中的心房颤动（AF）迅速转为窦性心律，且在正常人体志愿者中安全且耐受良好。
我们研究了氟卡尼经肺部给药对心房和心室去极化和复极化持续时间的影响。
在 12 只闭合胸腔的麻醉约克夏猪中，通过位于主支气管分叉处的导管进行气管内滴注（1.5mg/kg，快速推注）氟卡尼或无菌水（安慰剂）。通过在右心房和左心室中放置导管并进行荧光透视定位，从导管中获得的高分辨率电图可避免由于快速心率缩短 TP 间隔时体表导联中 P 波和 T 波融合而导致的测量误差。通过右心房导管电极传递电刺激来实现起搏。
在窦性心律（98±4.7 次/分钟）下，气管内氟卡尼给药可使心房去极化（P）持续时间分别增加 22%（39.8±3.2 至 48.7±3.3 毫秒）和左心室（LV）QRS 波群持续时间增加 20%（47.9±1.6 至 57.3±1.8 毫秒），在给药后 2 分钟达到峰值效应。在 180 次/分钟的右心房起搏下，P 持续时间增加了 55%（37.0±2.0 至 57.2±1.6 毫秒；P<0.0001）。心房反应大于 LV QRS 波群持续时间的 30%增加（46.6±1.7 至 60.6±2.5 毫秒；P=0.001）。安慰剂对起搏时的 P 持续时间和 QRS 波群持续时间没有影响（两者 P≥0.4）。心房复极持续时间（PT；P=0.46）和 QT 间期（P=0.49）保持不变。
气管内氟卡尼对心房去极化持续时间的作用比心室快，呈速率依赖性，与心室去极化持续时间相比。氟卡尼经肺部给药可能有助于将 AF 转为窦性心律，同时降低心室致心律失常风险。
