Intracellular calcium dynamics and anisotropic reentry in isolated canine pulmonary veins and left atrium
Intracellular calcium dynamics and anisotropic reentry in isolated canine pulmonary veins and left atrium
复制标题
DOI：
10.1161/circulationaha.104.498758
复制
发表时间：
2005-06-07
期刊：
影响因子：
37.8
通讯作者：
Chen, PS
中科院分区：
文献类型：
--
作者：
Chou, CC;Nihei, M;Chen, PS
背景-肺静脉 (PV) 心房颤动 (AF) 期间经常出现由于局灶放电或折返导致的快速激活。这些快速激活的机制尚不清楚。方法和结果 - 我们研究了 7 个分离的、Langendorff 灌注的犬左心房 (LA) 和 PV 制剂，并使用 2 个相机单独绘制膜电位 (Vm, n = 3) 或同时绘制 Vm 和细胞内钙 (Ca-i, n = 4)。快速心房起搏引起 5 只狗近端 PV 局灶性放电 26 次。兰尼定输注期间的周期长度为 223 +/- 52 毫秒 (n = 13)，兰尼定加异丙肾上腺素输注期间的周期长度为 133 +/- 59 毫秒 (n = 13)。在 2 种制剂的 6 次发作中，Ca-i 的升高先于局部放电部位的 Vm 激活，这与电压无关的自发 Ca-i 释放相一致。起搏引起的折返过程中的相位奇点特别聚集在 PV-LA 交界处。过碘酸希夫 (PAS) 染色可识别出沿 PV 肌袖心内膜的大细胞，细胞质呈浅色。心肌纤维方向发生突变，PV 和 PV-LA 交界处间质纤维化增加。结论：PV 肌袖可能出现电压无关的 Cai 释放，导致局灶性放电。与节点样细胞相容的 PAS 阳性细胞的存在也可能促进局灶放电。在再入过程中，相奇点优先聚集在各向异性增加的位置，例如 PV-LA 连接处。这些发现表明，自发钙释放和各向异性折返引起的局灶放电都有助于 AF 期间 PV 的快速激活。
Background-Rapid activations due to either focal discharge or reentry are often present during atrial fibrillation (AF) in the pulmonary veins (PVs). The mechanisms of these rapid activations are unclear.Methods and Results-We studied 7 isolated, Langendorff-perfused canine left atrial (LA) and PV preparations and used 2 cameras to map membrane potential alone (Vm, n = 3) or Vm and intracellular calcium simultaneously (Ca-i, n = 4). Rapid atrial pacing induced 26 episodes of focal discharge from the proximal PVs in 5 dogs. The cycle lengths were 223 +/- 52 ms during ryanodine infusion (n = 13) and 133 +/- 59 ms during ryanodine plus isoproterenol infusion (n = 13). The rise of Ca-i preceded Vm activation at the sites of focal discharge in 6 episodes of 2 preparations, compatible with voltage-independent spontaneous Ca-i release. Phase singularities during pacing-induced reentry clustered specifically at the PV-LA junction. Periodic acid-Schiff (PAS) stain identified large cells with pale cytoplasm along the endocardium of PV muscle sleeves. There were abrupt changes in myocardial fiber orientation and increased interstitial fibrosis in the PV and at the PV-LA junction.Conclusions-PV muscle sleeves may develop voltage-independent Cai release, resulting in focal discharge. Focal discharge may also be facilitated by the presence of PAS-positive cells that are compatible with node-like cells. During reentry, phase singularities clustered preferentially at sites of increased anisotropy such as the PV-LA junction. These findings suggest that focal discharge caused by spontaneous calcium release and anisotropic reentry both contribute to rapid activations in the PVs during AF.