Correlation between pharmacological binding properties of IKur inhibitors and antiarrhythmic efficiency in a virtual model of cronical atrial fibrillation
The block of IKur is a promising approach in the pharmacotherapy of atrial fibrillation (AF). Numerous pharmaceutical companies investigate specific IKur-inhibitors. Advantage of a selective IKur-inhibition is an atrial action potential duration prolongation without ventricular side effects. The clinical and experimental data published so far are however unconvincing. Possible reason for the missing effectiveness on the one hand could be remodeling processes of the atrial myocardium (IKur-reduction); on the other hand pharmacological characteristics (kinetics of the pharmacological block) could also play an important role. Tsujimae et al. showed differential effects of a simulated IKur-block with different pharmacological characteristics on action potential duration in an „in-silico“ model of atrial cardiomyoctes. Further-more, differences of the simulated inhibitors in healthy cells and cells effected by AF typical remodeling was demonstrated.
In this computer-based study, the hypothesis should be examined that the pharmacological characteristics of IKur-inhibitors play an important role for the therapeutic success for the ter-mination of re-entry excitations in the human atrium under chronically AF.