QT延長症候群２型における早期後脱分極を介した致死性不整脈の発生メカニズム：in silico 研究

抄録

Reentry is a basic mechanism of cardiac arrhythmias. In particular, torsades de pointes (TdP) is a spiral excitation wave reentry that meanders through the ventricles. Based on clinical studies showing that early afterdepolarization (EAD) precedes the development of TdP in patients with long QT syndrome type II, it has been suggested that ventricular arrhythmias are triggered by the development of EAD mediated by excessive prolongation of the action potential of ventricular myocytes inducing QT prolongation in ECG. However, the role of EAD in the generation of TdP remains unclear. In the present study, we investigated the relationship between EAD and TdP initiation by constructing a 6 × 6 cm (600 × 600 units) myocardial sheet model consisting of a human ventricular myocyte model (Kurata et al., Biophys J, 2005) and performing simulations of excitation propagation. The EADs were assumed to occur in islands (clusters) in the ventricular tissue, and the relationship between the change in the number of EAD clusters and the spiral excitation wave (TdP) initiation was investigated. In the case of a single island (400 x 400 unit EAD cluster), spiral excitation wave initiations did not occur. On the other hand, spiral excitation waves were caused by dividing the 400 × 400 unit EAD cluster into 4, 9, and 16 islands. However, no spiral excitation occurred in the 25 clusters. This suggests that not only the spatial distribution of EAD clusters but also the cluster size influences the TdP initiation. Clustering EAD-evoked cardiomyocytes and discontinuous distributions of the clusters may promote the TdP initiation, i.e., may increase the risk for lethal arrhythmia in patients with LQT2.