Electrical Control of Reentrant Spiral Waves in Cardiac Tissue

描述（由申请人提供）：功能性折返性兴奋波（螺旋波）是心脏组织中纤颤和多种形式快速性心律失常的基础。目前，强电脉冲或恒定的低能量脉冲序列被用于终止这些心律失常，并且在临床试验中已经显示出在降低死亡率方面非常有效。将在培养的大鼠心室肌细胞单层中研究低能量脉冲可以改善这些波的控制的程度。将使用电压敏感染料和多位点光学映射监测单层的电活性。我们实验室以前的工作已经证明，在这个实验模型中可以重现完整心脏中已知的折返模式。将在单层上施加均匀和非均匀电场，以量化电场赋予自由旋转螺旋波漂移和方向的能力。将测试直流和交流场脉冲，目的是开发可用于引导螺旋波的最佳波形。我们还将测试用于控制固定在小解剖障碍物上的螺旋波动力学的各种策略。脉冲电场将用于减慢周期长度并破坏钉扎力，从而将螺旋波从锚定部位驱逐。我们假设在再入周期内存在一个最佳的时间窗口，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将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，我们将测试螺旋波的电场控制是否在细胞-细胞耦合受损的组织中被加重，如发生在梗死后或老化期间。由于大量的锚定位点，现在可用于钉在这样的组织基板的螺旋波，我们将开发算法，重复分离和转向螺旋波在所需的方向。该项目的成果将构成一个原理证明，即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特性，例如漂移、周期长度和锚定位置的附着。成功地使用低能量对抗可以避免当今高能量治疗的痛苦和心理创伤。

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.