Beth Israel Deaconess Medical Center, Boston, MA, United States of America; Department of Environmental Sciences, Harvard School of Public Health, Boston, MA, United States of America; Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
InCarda Therapeutics, Inc., Newark, CA, United States of America.
Int J Cardiol. 2019 Jan 1;274:170-174. doi: 10.1016/j.ijcard.2018.09.029. Epub 2018 Sep 8.
We investigated whether rapid administration of a low dose of flecainide, either intratracheally or intravenously (IV), could accelerate conversion of atrial fibrillation (AF) while reducing adverse ventricular effects.
Flecainide was delivered via intratracheal administration at 1.5 mg/kg bolus and compared to IV infusion at 1.0 mg/kg over 2 min (lower-dose, rapid) and 2.0 mg/kg over 10 min (ESC guideline) in closed-chest, anesthetized Yorkshire pigs. Catheters were fluoroscopically positioned in right atrium to measure atrial depolarization (P) duration and left ventricle (LV) to measure QRS complex duration and contractility (LV dP/dt) during atrial pacing at 140 beats/min. Flecainide was delivered intratracheally via a catheter positioned at the bifurcation of the main bronchi. AF was induced by intrapericardial administration of acetylcholine followed by burst pacing.
Flecainide reduced AF duration similarly by intratracheal and IV delivery. Peak plasma levels were comparable but T differed and coincided with peaks in P prolongation. The area under the curve indicating sustained plasma levels was greater for higher-dose, slow IV flecainide than for either intratracheal instillation (by 32%) or lower-dose, rapid IV infusion (by 88%). As a result, higher-dose, slow IV flecainide caused 58% (p < 0.03) and 48% (p < 0.006) greater increases in QRS complex duration and 61% and 96% (both, p < 0.02) greater reductions in contractility compared to intratracheal and lower-dose, rapid IV flecainide, respectively.
Lower-dose, rapid flecainide, delivered either intratracheally or IV, optimizes the plasma concentration profile for effective conversion of AF while minimizing adverse effects on QRS complex duration and LV contractility.
我们研究了经气管内或静脉内（IV）快速给予低剂量氟卡尼是否可以加速心房颤动（AF）的转复，同时减少不良的心室效应。
在闭胸、麻醉的约克夏猪中，氟卡尼经气管内给予 1.5mg/kg 推注，并与 IV 输注 1.0mg/kg 持续 2 分钟（低剂量、快速）和 2.0mg/kg 持续 10 分钟（ESC 指南）进行比较。在心房起搏 140 次/分时，导管在右心房内定位以测量心房去极化（P）持续时间，在左心室（LV）内定位以测量 QRS 复合体持续时间和收缩性（LV dP/dt）。氟卡尼通过置于主支气管分叉处的导管经气管内给予。通过心包内给予乙酰胆碱诱导 AF，然后进行爆发式起搏。
氟卡尼经气管内和 IV 给药均可相似地缩短 AF 持续时间。峰值血浆水平相当，但 T 不同，与 P 延长的峰值一致。表明持续血浆水平的曲线下面积，对于高剂量、缓慢 IV 氟卡尼，高于气管内滴注（高 32%）或低剂量、快速 IV 输注（高 88%）。结果，高剂量、缓慢 IV 氟卡尼使 QRS 复合体持续时间分别增加 58%（p<0.03）和 48%（p<0.006），收缩性分别降低 61%和 96%（均为 p<0.02），与气管内和低剂量、快速 IV 氟卡尼相比。
低剂量、快速氟卡尼，经气管内或 IV 给予，优化了有效转复 AF 的血浆浓度曲线，同时最小化了对 QRS 复合体持续时间和 LV 收缩性的不良影响。
