An experimental study for the mechanism of atrial fibrillation and its control by means of optical imaging of cell-to-cell communication

心房颤动是一种危及生命的疾病，可增加血栓形成和心力衰竭的风险。这种心律失常有许多可能的机制，如异位自动性、再入、传导衰竭等，但尚未阐明。由于心房由多种类型的细胞组成，包括心肌细胞、内皮细胞、成纤维细胞、血管平滑肌细胞等，原始组织中细胞活动的成像似乎是研究心房心律失常的合适手段。在这项工作中，我们可视化了心房组织中的细胞活动，并研究了心房颤动的机制。心房肌取自猪或豚鼠心脏，并加载Rhod-2和/或Di-4-ANEPPS。利用共聚焦显微镜系统获得二维荧光信号。我们发现心房肌有一些明显的特征。首先，在大多数心房肌中，Ca^<2+>波与动作电位诱导的Ca^<2+>瞬态同时发生。这意味着延迟去极化后（DAD）不会发生在这些肌细胞中。相反，早期后去极化（EAD）可能是触发的原因。心房大部有活动。其次，Ca^<2+>瞬态在单个细胞内经常交替，这与心室细胞的Ca^<2+>瞬态在细胞间交替而不是在单个细胞内形成鲜明对比。由于交替被认为是传导异常的原因，因此EC耦合能力较弱和频繁的交替可能是心房再入概率高的原因。最后，这里开发的程序似乎也适用于室性心律失常的研究。

Atrial fibrillation is a life-threatening disease that increases a risk of thrombus formation and heart failure. There are many possible mechanisms for this arrhythmia such as ectopic automaticity, reentry, conduction failure, etc., and they have yet to be elucidated. Because the atrium is composed of multiple types of cells including cardiac myocytes, endothelial cells, fibroblasts, vascular smooth muscle cells and so on, imaging of cellular activities in original tissues seems to be appropriate means for studies of atrial arrhythmias. In this work, we visualized cellular activities in atrial tissues and studied the mechanisms of atrial fibrillation.Atrial muscles were obtained from pig or guinea pig hearts and loaded with Rhod-2 and/or Di-4-ANEPPS. Two-dimensional fluorescence signals were obtained using a confocal microscope system. We found some distinct characteristics of atrial muscles. Firstly, in most of atrial muscles, Ca^<2+> waves occurred at the same time as initiation of action potential-induced Ca^<2+> transients. This means that delayed afterdepolarization (DAD)cannot occur in those myocytes. Instead, early afterdepolarization (EAD) may be a cause of triggered. Activity in most part of atrium. Secondly, Ca^<2+> transients often alternate within individual cells, which is in marked contrast to ventricular cells where Ca^<2+> transients alternated between cells but not within single cells. Because the alternans has been suggested to be a cause of abnormal conduction, the less EC coupling ability and frequent alternans may be reasons for high probability of reentry in atrium. Finally, the procedure developed here appeared to be also useful for studies of ventricular arrhythmia.