Activation of inward rectifier potassium channels accelerates atrial fibrillation in humans -: Evidence for a Reentrant mechanism
Activation of inward rectifier potassium channels accelerates atrial fibrillation in humans -: Evidence for a Reentrant mechanism
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DOI：
10.1161/circulationaha.106.633735
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发表时间：
2006-12-05
期刊：
影响因子：
37.8
通讯作者：
Berenfeld, Omer
中科院分区：
文献类型：
--
作者：
Atienza, Felipe;Almendral, Jesus;Berenfeld, Omer
背景：目前尚不清楚人类心房颤动（AF）的驱动因素是局灶性还是再入性。为了验证功能性再入参与人类房颤维持的假设，我们测定了腺苷输注对不同心房部位局部优势频率（DF）的影响。通过增加向内整流钾通道电导，腺苷会增加可重入驱动器的DF，但在焦点机制的情况下会降低DF。方法与结果：对33例房颤患者（21例为阵发性房颤，12例为持续性房颤）进行研究，记录肺静脉-左心房交界、右高心房和冠状窦的记录。在基线和腺苷效应峰值时测定DFs。在阵发性房颤中，与基线相比，腺苷增加了各区域的最大DF (PV-LAJ, 8.03 +/- 2.2 vs 5.7 +/- 0.8；右高心房，7 +/- 2.2 vs 5.4 +/- 0.7；冠状窦，6.6 +/- 1.1 vs 5.3 +/- 0.7 Hz； P=0.001)，增加了左至右DF梯度（P=0.007）。相比之下，在持续性房颤中，腺苷仅在右高心房增加DF （8.33 +/- 1.1 vs 6.8 +/- 1.2 Hz； P=0.004）。在4例阵发性房颤患者中，实时DF制图确定了PV-LAJ附近DF最高的位点，腺苷诱导DF增加（6.7 +/- 0.29 vs 4.96 +/- 0.26 Hz； P=0.008）。最后，仿真表明，可重入驱动器的频率与腺苷调制的内向整流钾电流成比例地加速。结论：与持续性人房颤相比，腺苷在阵发性房颤中加速驱动因子和增加频率的方式不同。结果强烈提示房颤是由再入源维持的，在阵发性房颤中最可能位于PV-LAJ，而在持续性房颤中更可能位于非pv位置。
Background-It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentrant. To test the hypothesis that functional reentry is involved in human AF maintenance, we determined the effects of adenosine infusion on local dominant frequency (DF) at different atrial sites. By increasing inward rectifier potassium channel conductance, adenosine would increase DF of reentrant drivers but decrease it in the case of a focal mechanism.Methods and Results-Thirty-three patients were studied during AF (21 paroxysmal, 12 persistent) using recordings from each pulmonary vein-left atrial junction (PV-LAJ), high right atrium, and coronary sinus. DFs were determined during baseline and peak adenosine effect. In paroxysmal AF, adenosine increased maximal DF at each region compared with baseline (PV-LAJ, 8.03 +/- 2.2 versus 5.7 +/- 0.8; high right atrium, 7 +/- 2.2 versus 5.4 +/- 0.7; coronary sinus, 6.6 +/- 1.1 versus 5.3 +/- 0.7 Hz; P=0.001) and increased the left-to-right DF gradient (P=0.007). In contrast, in persistent AF, adenosine increased DF only in the high right atrium (8.33 +/- 1.1 versus 6.8 +/- 1.2 Hz; P=0.004). In 4 paroxysmal AF patients, real-time DF mapping of the left atrium identified the highest DF sites near the PV-LAJ, where adenosine induced an increase in DF (6.7 +/- 0.29 versus 4.96 +/- 0.26 Hz; P=0.008). Finally, simulations demonstrate that the frequency of reentrant drivers accelerates proportionally to the adenosine-modulated inward rectifier potassium current.Conclusions-Adenosine accelerates drivers and increases frequency differently in paroxysmal compared with persistent human AF. The results strongly suggest that AF is maintained by reentrant sources, most likely located at the PV-LAJ in paroxysmal AF, whereas non-PV locations are more likely in persistent AF.