The Role of Diastolic Outward Current Deactivation Kinetics on the Induction of Spiral Waves

The mechanism of induced reentry in an initially homogeneous repolurization matrix still remains undefined, In the present study we hypothesized that the slow deactivation rate of the delayed outward current (dIo/dt), which occurs during diastole after complete repolarizafion, can cause activation failure and facilitate reentry. We modeled the excitation-recovery process using the modified FilzHugh-Nagumo equations in a two-dimensional medium of 128 by 128 cells using the Connection Machine (CM-2), a massively parallel computer that is highly suitable for this class of problem. The model was one cell thick, uniformly excitable, and isofropic. When (he rate of Io deactivation was slowed to yield action potential duration (APD) restitution curves similar to experimentally observed arrhythmic ventricular muscle cells APD restitution curves, premature stimulation (S₂) induced nonstationary double spiral waves (Figure 8 reentry). A decrease in d/o/dt increased the radius of the circle around which the iip of the spiral waves rotates and decreased its angular velocity. Wave fronts propagated through areas where the residual dia-stolic Io was fully inactivated and blocked in areas where its amplitude was high. No such dynamics of wave front propagation could be induced when S₂ was applied after the completion of lo deactivation. We conclude that the kinetics of deactivation of the Io during diastole has a profound influence on the dynamics of two-dimensional wave front propagation. The similarities of the APD restitution curve implemented in the computer model with slow deactivation of Io and that observed in our canine model of quinidine induced ventricular fachyarrhythmias suggest that Io deactivation kinetics may play an important role in arrhythmogenesis in the intact ventricle.