Transition from ventricular fibrillation to ventricular tachycardia: a simulation study on the role of Ca2+-channel blockers in human ventricular tissue

Abstract

We study the effect of blocking the L-type Ca2+-channel on fibrillation in simulations in two-dimensional (2D) isotropic sheets of ventricular tissue and in a three-dimensional anisotropic anatomical model of human ventricles, using a previously developed model of human ventricular cells. Ventricular fibrillation (VF) was obtained as a result of spiral wave breakup and consisted of a varying number of chaotically wandering wavelets activating tissue at a frequency of about 6.0 Hz. We show that blocking the Ca2+-current by 75% can convert ventricular fibrillation into a periodic regime with a small number of stable spiral waves, ranging from six in 2D sheets of 25 × 25 cm to a single spiral in the anatomical model of human ventricles. The dominant frequency during this process changed to about 10.0 Hz in the 2D simulations, but to only 5.0 Hz in the whole heart simulations where a single spiral wave anchored around an anatomical obstacle. We show that the observed effects were due to a flattening of the electrical restitution curve, which prevented the generation of wave breaks and stabilized the activation patterns.