Can anodal stimulation contribute to cardiac resynchronization?

In order to increase intraventricular synchronization, dual-site activation of the left ventricle (LV) could be achieved by a bipolar lead capable of both cathodal and anodal capture. However, anodal pulses might imply a higher arrhythmic risk than cathodal pulses, due to a lower threshold in the vulnerable period. In the aim of increasing LV stimulation safety, we studied end-diastolic anodal activation in the rat heart. Epicardial isopotential and isochrone maps revealed two mechanisms of anodal excitation: i) at threshold, at the pacing site, after 5-12 ms from the pulse onset (anode break); ii) at higher current intensities after 3-5 ms (anode make), in two symmetric regions 1 mm from pacing site along fibres, corresponding to the virtual cathodes of the bidomain model. Whole cell patch clamp demonstrated that break excitation is mainly sustained by a depolarizing current activated in hyperpolarization (ih), which slowly deactivates after the pulse offset. Break excitation is likely to explain the reduced anodal threshold in the vulnerable period. Stimulation modalities that could prevent the anode break response, while still allowing “make” activation in the virtual cathodes, are under investigation.