Effects of atrial muscle structure on the initiation mechanism of atrial fibrillation and its drug therapy

用高分辨率光学标测技术测量右心房游离壁右侧心外膜和心内膜的动作电位，观察到跨壁复极梯度的变化。这些都是在对照条件下，在右肺静脉-心房交界处的脂肪垫电刺激(即心内副交感神经刺激)和乙酰胆碱(ACh)输注期间进行的。与对照组相比，心内副交感神经刺激和ACh注射期间跨室壁复极梯度没有增加。在ACh注射过程中，阵发性快速性心律失常(AT)是由单一的早搏刺激引起的，并与局灶性激动模式有关(84%)。重要的是，当复极梯度较小时，心内副交感神经刺激时AT的启动也与无传导阻滞的局部活动模式(36%)相关。在…期间心内副交感神经刺激较多，当复极梯度较大时，常可观察到传导阻滞和不完全大折返模式(%)。在注射垂体腺苷激活肽的过程中，心房表面和跨内侧的复极梯度较小，单个早搏刺激引起的房速与无传导阻断的局灶性激动(100%)有关。这些结果提示，心房组织复杂的组织结构对房性心动过速的局灶性发作具有重要作用。我们用延迟整流钾电流阻滞剂的快速激活成分E-4031和超极化激活电流阻滞剂扎替布拉丁研究了离子电流密度的空间变化。E-4031使右房游离壁动作电位时程增加幅度大于左房肺静脉区。相比之下，Zatebradine同样增加了他们之间的时差。这些结果提示了心房离子电流的区域性差异。较少

In isolated arterially perfused canine atria, transmural repolarization gradients were observed using high resolution optical mapping techniques to measure action potentials from the epicardial and endocardial surface on the right at rial free wall. These are performed during control conditions, during electrical stimulation of the fat pad at the right pulmonary vein-atrial junction (i.e. intracardiac parasympathetic stimulations) and during acetylcholine (ACh) infusion. Transmural repolarization gradients did not increase during intracardiac parasympathetic stimulation and during ACh infusion compared to during control. During ACh infusion, at rial tachyarrhythmia (AT) was initiated with a single premature stimulus and was associated with a focal pattern of activation (84 %). Importantly, AT initiation during intracardiac parasympathetic stimulations was also associated with the focal pattern of activity (36 %) without conduction block when repolarization gradients were small. During … More intracardiac parasympathetic stimulations, however, when repolarization gradients were large, patterns of conduction block and incomplete macroreentry were often observed (64 %). During pituitary adenylate activating polypeptide injection, repolarization gradients were small across the atrial surface and transmirally and a single premature stimulus initiated AT which was associated with a focal pattern of activation (100 %) without conduction block. These results suggest that the complicated tissue structure of atrial tissue has an important role for initiating focal pattern of AT. We examined the spatial variation in ionic current density us ing E-4031, the rapidly activating component of delayed rectifier potassium current blocker, and Zatebradine, hyperpolarization activated-current blocker. E-4031 increased action potential duration (APD) greater in the right atrial free wall than in the pulmonary vein area of left atrium. In contrast, Zatebradine equally increased APD between them. These results suggest the regional variation in atrial ionic currents. Less