Phase Space Approach for Quantification of Arrhythmia Caused by Regional Potassium Level Heterogeneities in Isolated Rabbit Hearts

Ilija Uzelac1 and flavio fenton2
1Georgia Institute of Technology, 2georgia tech


Aims: Spatial myocardium heterogeneities in terms of elevated extracellular potassium (K+) levels affect electrophysiological parameters, and are substrate for wave-blocks and reentry initiation. However, the particular role of K+ level imbalances and dispersion necessary for arrhythmogenesis still remains poorly understood. In this study, we use optical mapping data and apply a phase space approach as a tool to quantify the role of regional elevated K+ levels in myocardium tissue and reentry initiation. Method: Isolated rabbit hearts were globally Langendorff perfused with Tyrode’s perfusate containing 4 mM of K+, and regionally perfused through left marginal artery cannulation with the perfusate K+ levels ranging 6 to 12 mM. Optical mapping measurements were performed using the Di-4-ANBDQPQ dye. To assess impact of K+ spatial heterogeneity, hearts were paced in burst pacing protocols ranging from 400 to 130 ms in 5 to 25 ms steps. In addition, hearts were stained with K+ fluorescent sensitive indicator PBFI for localization of K+ elevated region.

Results: Faster pacing rates induced action potential (AP) alternans, which were more pronounced, and gradually increased along wavefront propagation in K+ elevated region, resulting in 2:1 conduction block and wavebreaks. To quantify role of K+ region, phase space maps were created by time embedding method from Vm optical mapping measurement. Wavebreaks were localized by calculating phase space singularities, and then spatially correlated with K+ level maps across the entire visualized heart surface. Spatial correlation of waveblocks was then assessed through phase space parametrization with different threshold levels. With faster pacing rates, electrophysiological heterogeneous areas with elevated K+ region expanded reaching the entire regions for K+ level elevation to 12mM when region was unexcitable.

Conclusions: Phase space approach is a viable tool for studying and quantification of arrhythmogenesis, opening novel avenues to study acute myocardial ischemia causing elevation of extracellular K+.