Abstract 5336: Mechanisms Responsible for Spatially Discordant Alternans in Transgenic Rabbit Model of LQT2
Spatially discordant alternans (SDA) increases dispersion of refractoriness and predisposes to arrhythmia. LQT2 transgenic rabbits (lacking IKr) have a higher incidence of spontaneous arrhythmias compared to Littermate controls (LMC). We investigated the mechanism of SDA in LQT2 and LMC rabbits. LMC and LQT2 hearts were retrogradely perfused and stimulated from the LV free wall. APD and conduction velocity (CV) were recorded from the anterior epicardial surface using di-4-ANEPPS with a high speed CMOS camera (100×100 pixels, 1000 frames/s). APD restitution was calculated and its dispersion was defined as |max-min| of slope. Mean slope of APD restitution was steeper in LQT2 compared to LMC (0.83 ± 0.13 vs. 0.64 ± 0.11) with a greater spatial dispersion of restitution slope across the anterior epicardial surface (1.1 vs. 0.24). Progression to SDA was frequent in LQT2 (5/7) compared to LMC (2/6). SDA was associated with alternating CV in both groups. Shorter stimulation CL caused a phase change in alternans (panel A: traces) and shift in location of discordance in both LMC and LQT2 (panel B:nodal line maps). However, LQT2 hearts demonstrated persistent complex beat-to-beat changes in discordance pattern (panel C&D: nodal line map), a behavior not predicted by the CV restitution hypothesis. In conclusion, CV alternans produces SDA in both LMC and LQT2 rabbits. However, high spatial heterogeneity in APD restitution in LQT2 rabbits also precipitates complex SDA patterns, possibly increasing vulnerability to arrhythmia in this model.