Spatiotemporal evolution and prediction of [Ca²⁺]_i and APD alternans in isolated rabbit hearts

Prediction of Alternans in the Heart Introduction Action potential duration (APD) alternans can be accompanied by alternans in intracellular calcium transients ([Ca²⁺]_i), leading to electromechanical alternans. Electromechanical alternans is considered a substrate for ventricular fibrillation. Although some techniques have been developed to predict APD alternans, the onset of [Ca²⁺]_i alternans has never been predicted. Methods and Results Simultaneous mapping of voltage and calcium was performed in 8 Langendorff-perfused rabbit hearts. APD, [Ca²⁺] _i amplitude (CaA) and duration (CaD) alternans were induced using a perturbed downsweep protocol. Local onset of alternans (B^onset) was defined as the cycle length (BCL) at which at least 10% of the RV exhibited alternans. We observed that the local onset of CaA alternans always occurred first, followed by APD and then CaD alternans. We constructed APD, CaD, and CaA restitution portraits for 2 regions of the heart defined at B^onset: the 1:1_alt region, which developed alternans, and the 1:1 region, which did not. Our results also show that the slopes S12 Max and S_Dyn were higher in 1:1_alt region (S_Dyn = 0.99 ± 0.04 vs 0.73 ± 0.06; S12 Max = 0.95 ± 0.13 vs 0.65 ± 0.1, P < 0.05) prior to onset of CaD alternans, while S₁₂ and S12 Max were significantly higher in the 1:1_alt region (S₁₂ = 0.59 ± 0.19 vs 0.19 ± 0.02; S12 Max = 1.09 ± 0.1 vs 0.61 ± 0.08, P < 0.05) prior to onset of CaA alternans. Conclusion We successfully applied the restitution portrait technique to the prediction of [Ca²⁺]_i (both CaA and CaD) alternans. The slopes of the APD/CaD/CaA restitution portrait are definitive indicators of APD, CaD, and CaA alternans.