Reexcitation mechanisms in epicardial tissue: Role of Ito density heterogeneities and I_Na⁺ inactivation kinetics.

Inma R.Cantalapiedra*, Angelina Peñaranda, Blas Echebarria

Departament de Física Aplicada, Universitat Politècnica de Catalunya, EPSEB, 44-50 Av. Dr. Marañón, 08028 Barcelona, Spain.

*inma@fa.upc.edu

Dispersion of action potential repolarization is known to be an important arrhythmogenic factor in cardiopathies such as Brugada syndrome. In this work, we analyze the effect of a variation in sodium current (I_Na⁺) inactivation and a heterogeneous rise of transient outward current (I_to) in the probability of reentry in epicardial tissue. We use the Luo–Rudy model of epicardial ventricular action potential to study wave propagation in a one-dimensional fiber. Spatial dispersion in repolarization is introduced by splitting the fiber into zones with different strength of Ito. We then analyze the pro-arrhythmic effect of a variation in the relaxation time and steady-state of the sodium channel fast inactivating gate h. We confirm (Cantalapiedra et al., 2009) that while Ito dispersion is necessary for phase-2 reentry, altered sodium inactivation kinetics influences the probability of reexcitation in a highly non linear fashion.

References

Cantalapiedra IR, Peñaranda A, Mont L, Brugada J, Echebarria B. Reexcitation mechanisms in epicardial tissue: Role of I_to density heterogeneities and I_Na inactivation kinetics. J. Theor. Biology 2009 (doi:10.1016/j.jtbi.2009.04.021)