Mechanisms of make and break excitation revisited: Paradoxical break excitation during diastolic stimulation

Onset and termination of electric stimulation may result in "make" and "break" excitation of the heart tissue. Wikswo et al. (30) explained both types of stimulations by virtual electrode polarization. Make excitation propagates from depolarized regions (virtual cathodes). Break excitation propagates from hyperpolarized regions (virtual anodes). However, these studies were limited to strong stimulus intensities. We examined excitation during weak near-threshold diastolic stimulation. We optically mapped electrical activity from a 4 × 4-mm area of epicardium of Langendorff-perfused rabbit hearts (n = 12) around the pacing electrode in the presence (n = 12) and absence (n = 2) of 15 mM 2,3-butanedione monoxime. Anodal and cathodal 2-ms stimuli of various intensities were applied. We imaged an excitation wavefront with 528-μs resolution. We found that strong stimuli (X5 threshold) result in make excitation, starting from the virtual cathodes. In contrast, near-threshold stimulation resulted in break excitation, originating from the virtual anodes. Characteristic biphasic up-strokes in the virtual cathode area were observed. Break and make excitation represent two extreme cases of near-threshold and far-above-threshold stimulations, respectively. Both mechanisms are likely to contribute during intermediate clinically relevant strengths.