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Keywords:

  • action potential;
  • alternans;
  • cycle length;
  • intracellular calcium;
  • optical mapping;
  • restitution

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 (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 inline image and SDyn were higher in 1:1alt region (SDyn = 0.99 ± 0.04 vs 0.73 ± 0.06; inline image = 0.95 ± 0.13 vs 0.65 ± 0.1, P < 0.05) prior to onset of CaD alternans, while S12 and inline image were significantly higher in the 1:1alt region (S12 = 0.59 ± 0.19 vs 0.19 ± 0.02; inline image = 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.