Zlochiver S, Johnson C, Tolkacheva E G
Department of Biomedical Engineering, Tel-Aviv University, Tel-Aviv 69379, Israel.
Department of Biomedical Engineering, University of Minnesota, Minneapolis 55455, USA.
Chaos. 2017 Sep;27(9):093903. doi: 10.1063/1.4999355.
Cardiac repolarization alternans describe the sequential alternation of the action potential duration (APD) and can develop during rapid pacing. In the ventricles, such alternans may rapidly turn into life risking arrhythmias under conditions of spatial heterogeneity. Thus, suppression of alternans by artificial pacing protocols, or alternans control, has been the subject of numerous theoretical, numerical, and experimental studies. Yet, previous attempts that were inspired by chaos control theories were successful only for a short spatial extent (<2 cm) from the pacing electrode. Previously, we demonstrated in a single cell model that pacing with a constant diastolic interval (DI) can suppress the formation of alternans at high rates of activation. We attributed this effect to the elimination of feedback between the pacing cycle length and the last APD, effectively preventing restitution-dependent alternans from developing. Here, we extend this idea into cable models to study the extent by which constant DI pacing can control alternans during wave propagation conditions. Constant DI pacing was applied to ventricular cable models of up to 5 cm, using human kinetics. Our results show that constant DI pacing significantly shifts the onset of both cardiac alternans and conduction blocks to higher pacing rates in comparison to pacing with constant cycle length. We also demonstrate that constant DI pacing reduces the propensity of spatially discordant alternans, a precursor of wavebreaks. We finally found that the protective effect of constant DI pacing is stronger for increased electrotonic coupling along the fiber in the sense that the onset of alternans is further shifted to higher activation rates. Overall, these results support the potential clinical applicability of such type of pacing in improving protocols of implanted pacemakers, in order to reduce the risk of life-threatening arrhythmias. Future research should be conducted in order to experimentally validate these promising results.
心脏复极交替现象描述了动作电位时程（APD）的顺序交替，并且在快速起搏过程中会出现。在心室中，在空间异质性条件下，这种交替现象可能会迅速转变为危及生命的心律失常。因此，通过人工起搏方案抑制交替现象，即交替现象控制，一直是众多理论、数值和实验研究的主题。然而，以往受混沌控制理论启发的尝试仅在距起搏电极较短的空间范围内（<2厘米）取得了成功。此前，我们在单细胞模型中证明，以恒定舒张间期（DI）进行起搏可以在高激活率下抑制交替现象的形成。我们将这种效应归因于消除了起搏周期长度与最后一个APD之间的反馈，从而有效地防止了依赖恢复的交替现象的发展。在此，我们将这一想法扩展到电缆模型中，以研究在波传播条件下恒定DI起搏能够控制交替现象的程度。使用人体动力学，将恒定DI起搏应用于长达5厘米的心室电缆模型。我们的结果表明，与以恒定周期长度起搏相比，恒定DI起搏显著地将心脏交替现象和传导阻滞的起始点转移到更高的起搏率。我们还证明，恒定DI起搏降低了空间不协调交替现象（波破碎的先兆）的倾向。我们最终发现，在沿纤维增加电紧张耦合的情况下，恒定DI起搏的保护作用更强，因为交替现象的起始点进一步转移到更高的激活率。总体而言，这些结果支持了这种起搏类型在改进植入式起搏器方案以降低危及生命的心律失常风险方面的潜在临床适用性。未来应开展研究以通过实验验证这些有前景的结果。
