Electrical Control of Reentrant Spiral Waves in Cardiac Tissue

描述（由申请人提供）：功能性再入兴奋波（螺旋波）是心脏组织中纤维性颤动和多种形式的速性心律失常的基础。目前，使用强电脉冲或低能量脉冲的恒定序列来终止这些心律失常，并已在临床试验中显示对降低死亡率非常有效。在培养的大鼠心室肌细胞单层中，将研究低能量脉冲对这些波的控制可以改善到何种程度。将使用电压敏感染料和多位点光学测绘来监测单层膜的电活动。我们实验室之前的工作已经证明，完整心脏的已知再入模式可以在这个实验模型中重现。均匀和非均匀电场将在单层上施加，以量化电场对自由旋转的螺旋波施加漂移和方向的能力。直流和交流磁场脉冲都将被测试，目的是开发一个可用于引导螺旋波的最佳波形。我们还将测试各种策略来控制螺旋波的动力学，这些螺旋波被钉在小的解剖障碍上。脉动电场将被用来减缓周期长度并破坏固定力，从而将螺旋波从锚定位置移开。我们假设在再入周期内存在一个最佳时间窗口，在此期间电场脉冲可以成功地分离波。此外，我们假设分离波所需的能量会随着障碍物尺寸的增加而增加，但可以通过优化脉冲波形来改善。最后，我们将测试在细胞-细胞耦合受损的组织中，电场对螺旋波的控制是否会增强，如发生在梗死后或衰老过程中。由于现在有大量的锚定位点可以将螺旋波固定在这样的组织基质上，我们将开发算法来重复分离螺旋波并将其转向所需的方向。该项目的结果将构成一个原理证明，当针对给定的螺旋波进行定制时，低能量电场可用于控制螺旋波的特性，如漂移、周期长度和对锚点的附着。低能量反击的成功应用可以避免目前高能量治疗带来的痛苦和心理创伤。

DESCRIPTION (provided by applicant): Functional reentrant waves of excitation (spiral waves) underlie fibrillation and many forms of tachyarrhythmia in cardiac tissue. At present, strong electrical pulses or constant trains of low energy pulses are used to terminate these arrhythmias, and have been shown in clinical trials to be very effective in reducing mortality. The extent to which control of these waves can be improved by low energy pulses will be investigated in monolayers of cultured rat ventricular myocytes. The electrical activity of the monolayers will be monitored using voltage-sensitive dyes and multisite optical mapping. Previous work from our lab has demonstrated that the known patterns of reentry in the intact heart can be recapitulated in this experimental model. Uniform and nonuniform electric fields will be applied across the monolayers to quantify the ability of electric fields to impart drift and direction to a freely rotating spiral wave. Both dc and ac field pulses will be tested, with the goal of developing an optimal waveform that can be used to direct the spiral wave. We will also test various strategies for controlling the dynamics of spiral waves that are pinned to small anatomical obstacles. Pulsatile electric fields will be used to slow the cycle length and to disrupt the pinning forces, thereby dislodging the spiral wave from the anchoring site. We hypothesize that there exists an optimal temporal window within the reentry cycle during which electric field pulses can successfully detach the wave. Furthermore, we hypothesize that the energy required to detach the wave will increase with increasing obstacle size, but can be ameliorated by optimizing the pulse waveform. Finally, we will test whether electric field control of spiral waves is accentuated in tissue in which cell-cell coupling has been compromised, as occurs post-infarct or during aging. Because of the large number of anchoring sites that are now available to pin a spiral wave in such a tissue substrate, we will develop algorithms for repetitively detaching and steering spiral waves in desired directions. The outcome of this project will constitute a proof-of-principle that low energy electric fields, when tailored to a given spiral wave, can be used to control spiral wave characteristics such as drift, cycle length, and attachment to anchoring sites. The successful use of low energy counterchecks can avoid the pain and psychological trauma of present day high energy therapy.