Effects of cardiac sodium channel mutations on the vulnerable period in heterogeneous vs homogeneous models of ventricular wall

In this study we compare the effects of Na⁺ channel mutations on vulnerable period (VP) in hetero- versus homogeneous model of ventricular wall. According to several articles, some Na⁺ channel mutations and class I antiarrhythmics prolong VP in homogeneous models and increase risk of reentrant arrhythmias. Here more realistic model is used by introducing physiological transmural heterogeneity into a one-dimensional cable of the Luo-Rudy model cells. We propose a generalized formula for VP and describe new phenomena pertaining to VP not reported with the uniform models. Our simulation results show that the homogeneous models cannot adequately reproduce the effects of loss of Na⁺ channel functions on VP. Differences in results are significant both qualitatively and quantitatively. The proarrhythmic effect may not be, therefore, due to extended VP.