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It is recognized that specific mutations in ion channels responsible for cellular repolarization underlie various forms of the short QT syndrome (SQTS). However, the functional effects of the intrinsic spatial heterogeneities, such as island-distribution of mid-cardiomyocytes (M island) in cardiac tissue on the electrical instability in SQTS are poorly understood. In this study, the effect of M island on the generation and maintenance of re-entrant waves was investigated by using ten Tusscher et al. model. This model was extended to include a description of the KCNQ1-linked short QT syndrome (SQT2). A two dimensional (2D) tissue model, representing a transmural slice, comprised of 100 × 400 cells, among which 35% cells were mid-cardiomyocytes, either distributed in island form (M island) or continuous band (M band), 25% were endocardial and the rest were epicardial cells. The simulation data predicted that in SQT2 re-entry was more easily initiated and sustained in the M island model than in the M band model. It illustrated the important role of the intrinsic spatial electrical heterogeneities of cardiac tissue in the increased incidence of ventricular fibrillation associated with short QT syndrome.

Functional Effects of Island:distribution of Mid:cardiomyocytes on Re:entrant Excitation Waves in the KCNQ1:linked Short QT Syndrome