PDF(Pubmed)
Abstract：
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, often evolving from paroxysmal episodes to persistent stages over an extended timeframe. While various factors contribute to this progression, the precise biophysical mechanisms driving it remain unclear. Here we explore how rapid firing of cardiomyocytes at the outlet of the pulmonary vein of the left atria can create a substrate for a persistent re-entry wave. This is grounded in a recently formulated mathematical model of the regulation of calcium ion channel density by intracellular calcium concentration. According to the model, the number of calcium channels is controlled by the intracellular calcium concentration. In particular, if the concentration increases above a certain target level, the calcium current is weakened to restore the target level of calcium. During rapid pacing, the intracellular calcium concentration of the cardiomyocytes increases leading to a substantial reduction of the calcium current across the membrane of the myocytes, which again reduces the action potential duration. In a spatially resolved cell-based model of the outlet of the pulmonary vein of the left atria, we show that the reduced action potential duration can lead to re-entry. Initiated by rapid pacing, often stemming from paroxysmal AF episodes lasting several days, the reduction in calcium current is a critical factor. Our findings illustrate how such episodes can foster a conducive environment for persistent AF through electrical remodeling, characterized by diminished calcium currents. This underscores the importance of promptly addressing early AF episodes to prevent their progression to chronic stages.
摘要：
心房颤动(AF)是最常见的心律失常,通常在延长的时间范围内从阵发性发作演变为持续阶段。虽然各种因素促成了这一进展，驱动它的确切生物物理机制尚不清楚。在这里，我们探讨了心肌细胞在左心房肺静脉出口处的快速放电如何为持续的再入波产生底物。这基于最近制定的细胞内钙浓度调节钙离子通道密度的数学模型。根据模型,钙通道的数量受细胞内钙浓度的控制。特别是,如果浓度增加到某个目标水平以上，钙电流减弱以恢复钙的目标水平。在快速起搏期间,心肌细胞的细胞内钙浓度增加，导致穿过肌细胞膜的钙电流大幅减少，这再次减少了动作电位的持续时间。在基于细胞的左心房肺静脉出口的空间分辨模型中，我们表明，动作电位持续时间的减少可以导致重返大气层。通过快速起搏启动，通常源于持续数天的阵发性房颤发作，钙电流的降低是一个关键因素。我们的研究结果说明了此类事件如何通过电重塑为持续性房颤营造有利的环境，以钙电流减少为特征。这强调了迅速解决早期AF发作以防止其进展为慢性阶段的重要性。
