Cherry Elizabeth M
School of Mathematical Sciences, Rochester Institute of Technology, Rochester, New York 14623, USA.
Chaos. 2017 Sep;27(9):093902. doi: 10.1063/1.4999354.
Alternans, a proarrhythmic dynamical state in which cardiac action potentials alternate between long and short durations despite a constant pacing period, traditionally has been explained at the cellular level using nonlinear dynamics principles under the assumption that the action potential duration (APD) is determined solely by the time elapsed since the end of the previous action potential, called the diastolic interval (DI). In this scenario, APDs at a steady state should be the same provided that the preceding DIs are the same. Nevertheless, experiments attempting to eliminate alternans by dynamically adjusting the timing of pacing stimuli to keep the DI constant showed that alternans persisted, contradicting the traditional theory. It is now widely known that alternans also can arise from a different mechanism associated with intracellular calcium cycling. Our goal is to determine whether intracellular calcium dynamics can explain the experimental findings regarding the persistence of alternans despite a constant DI. For this, we use mathematical models capable of producing alternans through both voltage- and calcium-mediated mechanisms. We show that for voltage-driven alternans, action potentials elicited from a constant-DI protocol are always the same. However, in the case of calcium-driven alternans, the constant-DI protocol can result in alternans. Reducing the strength of the calcium instability progressively reduces and finally eliminates constant-DI alternans. Our findings suggest that screening for the presence of alternans using a constant-DI protocol has the potential for differentiating between voltage-driven and calcium-driven alternans.
交替现象是一种致心律失常的动力学状态，在此状态下，尽管起搏周期恒定，但心脏动作电位的持续时间会在长和短之间交替变化。传统上，在动作电位持续时间（APD）仅由自前一个动作电位结束以来所经过的时间（即舒张间期，DI）决定这一假设下，已使用非线性动力学原理在细胞水平对交替现象进行了解释。在这种情况下，只要先前的舒张间期相同，稳态下的动作电位持续时间就应该相同。然而，试图通过动态调整起搏刺激的时间以保持舒张间期恒定来消除交替现象的实验表明，交替现象仍然存在，这与传统理论相矛盾。现在人们普遍知道，交替现象也可能源于与细胞内钙循环相关的不同机制。我们的目标是确定细胞内钙动力学是否能够解释尽管舒张间期恒定但交替现象仍持续存在的实验结果。为此，我们使用能够通过电压介导和钙介导机制产生交替现象的数学模型。我们表明，对于电压驱动的交替现象，由恒定舒张间期方案引发的动作电位总是相同的。然而，在钙驱动的交替现象中，恒定舒张间期方案可能会导致交替现象。降低钙不稳定性的强度会逐渐减少并最终消除恒定舒张间期交替现象。我们的研究结果表明，使用恒定舒张间期方案筛查交替现象的存在有可能区分电压驱动和钙驱动的交替现象。
