Role of conduction velocity restitution and short-term memory in the development of action potential duration alternans in isolated rabbit hearts

Background - Spatially discordant alternans (SDA) has been linked to life-threatening arrhythmias. The mechanisms underlying SDA development in cardiac tissue remain unclear. Methods and Results - We investigated the role of conduction velocity (CV) restitution and short-term memory in the organization and evolution of alternans in action potential duration using high-resolution optical mapping of the epicardial surface in 8 isolated, Langendorff-perfused rabbit hearts. To assess the spatial organization of alternans, we tracked the evolution of nodal lines that separate out-of-phase regions of SDA. We measured the action potential duration heterogeneity index and maximal slope of CV restitution and estimated the effects of short-term memory by calculating time constant of action potential duration accommodation (tau). We found that 2 mechanisms underlie the development of SDA in the heart, leading to 2 distinct behaviors of nodal lines. The first mechanism is based on steep CV restitution and is associated with small tau and stable nodal lines. The second mechanism is associated with short-term memory ( large tau) and is characterized by shallow CV restitution and unstable behavior of nodal lines. The maximum slope of the CV restitution was steeper (18.16 +/- 3.34 m/s(2)) and tau was smaller (tau=4.31 +/- 0.33 stimuli) for areas with stable nodal lines than for areas with unstable nodal lines (6.32 +/- 0.96 m/s(2) and tau=10.3 +/- 1.84 stimuli; P < 0.01). Conclusions - Our results provide new insight into the mechanisms underlying SDA formation in the rabbit heart. Specifically, our results suggest that a new mechanism associated with short-term memory underlies SDA formation in the heart, in addition to steep CV restitution.