Depolarization diffusion during weak suprathreshold stimulation of cardiac tissue

Background: The theory of stimulation of cardiac tissue based on virtual electrode (VE) polarization was presented by Wikswo and his group (Wikswo, Biophys. J., 1995). Four basic regimes were distinguished: anodal make, anodal break, cathodal make, and cathodal break. We sought to determine applicability of this theory for near-threshold stimulus intensities. Methods: For the experiments we used fluorescence optical imaging to map virtual electrode polarization at the epicardium of Langendorff-perfused rabbit hearts stained with voltage-sensitive dyes. Unipolar cathodal pacing was applied during diastole via a platinum-iridium electrodes. Results: During near-threshold cathodal make stimulation we found deviations from Wikswo's theory. We observed that after quick virtual electrode polarization activation starts at hyperpolarized regions and then causes a subsequent activation of the depolarized regions. Such an activation pattern appears similar to break activation. The effect of the depolarization diffusion from depolarized to hyperpolarized regions of the VE obtained by us experimentally was confirmed theoretically by 2D active bidomain simulations. Conclusions: For weak near-threshold stimuli the activation pattern does not fit completely into the established model of Roth and Wikswo thus revealing its limitations.