Spatiotemporal Evolution and Prediction of [Ca2+]i and APD Alternans in Isolated Rabbit Hearts
This work was supported by National Science Foundation grants PHY 095 7468 (E.G.T), CMMI-1233951 (E.G.T) and CMMI-1234155 (X.Z.)
Prediction of Alternans in the Heart
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 (Bonset) 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 Bonset: the 1:1alt region, which developed alternans, and the 1:1 region, which did not. Our results also show that the slopes and SDyn were higher in 1:1alt region (SDyn = 0.99 ± 0.04 vs 0.73 ± 0.06; = 0.95 ± 0.13 vs 0.65 ± 0.1, P < 0.05) prior to onset of CaD alternans, while S12 and were significantly higher in the 1:1alt region (S12 = 0.59 ± 0.19 vs 0.19 ± 0.02; = 1.09 ± 0.1 vs 0.61 ± 0.08, P < 0.05) prior to onset of CaA alternans.
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.