Electrical Control of Reentrant Spiral Waves in Cardiac Tissue

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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.