Berenfeld Omer
Center for Arrhythmia Research. University of Michigan, Ann Arbor, MI, USA.
Arch Cardiol Mex. 2010 Oct-Dec;80(4):301-14.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans, however its mechanisms are poorly understood and its therapy is often sub-optimal. This article reviews recent experimental, numerical and clinical data on dynamics of wave propagation during AF and its mechanistic link to ionic and structural properties of the atria. At the onset, the article presents numerical and optical mapping data suggesting that a presence of periodic source with increasingly high dominant frequency (DF) of excitation underlies observations of dispersion of local activation rate during AF. Further optical mapping studies in isolated normal sheep hearts in the presence of acetylcholine (ACh) reveals that rotors localized to the left atrium (LA) drive the arrhythmia and are faster than those in the right atrium (RA). Patch-clamp data from isolated cardiomycytes shows that the ACh-modulated potassium inward rectifier current is higher in the LA than in the RA which may explain the higher DFs and sensitivity of LA rotors to ACh compared with RA rotors. Following, the role of fibrosis in governing the propagation dynamics with a decrease in excitation frequency is presented in AF in failing sheep hearts and complex activation in cell cultures. Translation into the clinical setting is then discussed: DF distribution in patients with paroxysmal AF follows the LA-to-RA gradients found in the acute cholinergic AF of sheep hearts with highest DFs localized primarily to the posterior LA wall and pulmonary veins (PV) region; however in patients with persistent AF, the highest DFs localize mainly outside of the PVs region with possible implication on the outcome of ablation procedures. Next, intravenous injection of adenosine to patients in AF is demonstrated to result in further acceleration of high DF sites and suggests that reentrant activity, rather than triggered or automatic activity, maintains the arrhythmia. Finally, analysis of excitation during AF developed in patients post-cardiac surgery suggests a DF distribution similar to that of patients with paroxysmal AF with dependency on fibrosis as found in sheep failing hearts and cell cultures. In sum, the article presents data demonstrating the use of DF of excitation in linking wave propagation mechanisms to ionic and structural properties in both experimental and human AF.
心房颤动（AF）是人类最常见的持续性心律失常，但其机制尚不清楚，治疗效果往往欠佳。本文综述了近期关于房颤期间波传播动力学及其与心房离子和结构特性的机制联系的实验、数值和临床数据。文章开篇介绍了数值和光学标测数据，表明存在具有越来越高的主导频率（DF）的周期性源是房颤期间局部激活率离散现象的基础。在乙酰胆碱（ACh）存在的情况下，对离体正常绵羊心脏进行的进一步光学标测研究表明，定位于左心房（LA）的转子驱动心律失常，且比右心房（RA）中的转子速度更快。来自离体心肌细胞的膜片钳数据显示，ACh调节的内向整流钾电流在LA中高于RA，这可能解释了与RA转子相比，LA转子具有更高的DF以及对ACh更敏感的原因。接下来，阐述了纤维化在衰竭绵羊心脏房颤中随着兴奋频率降低而控制传播动力学的作用以及细胞培养中的复杂激活情况。然后讨论了向临床的转化：阵发性房颤患者的DF分布遵循在绵羊心脏急性胆碱能房颤中发现的从LA到RA的梯度，最高DF主要定位于LA后壁和肺静脉（PV）区域；然而，在持续性房颤患者中，最高DF主要定位于PV区域之外，这可能对消融手术的结果产生影响。接下来，向房颤患者静脉注射腺苷被证明会导致高DF部位进一步加速，并表明折返活动而非触发或自动活动维持心律失常。最后，对心脏手术后患者发生的房颤期间的兴奋分析表明，DF分布与阵发性房颤患者相似，且与衰竭绵羊心脏和细胞培养中发现的对纤维化的依赖性相同。总之，本文提供的数据表明，在实验性和人类房颤中，利用兴奋的DF将波传播机制与离子和结构特性联系起来。
