Quiñonez Uribe Raúl A, Luther Stefan, Diaz-Maue Laura, Richter Claudia
RG Biomedical Physics, Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany.
Institute for Nonlinear Dynamics, Georg-August University, Göttingen, Germany.
Front Physiol. 2018 Nov 27;9:1651. doi: 10.3389/fphys.2018.01651. eCollection 2018.
Complex spatiotemporal non-linearity as observed during cardiac arrhythmia strongly correlates with vortex-like excitation wavelengths and tissue characteristics. Therefore, the control of arrhythmic patterns requires fundamental understanding of dependencies between onset and perpetuation of arrhythmia and substrate instabilities. Available treatments, such as drug application or high-energy electrical shocks, are discussed for potential side effects resulting in prognosis worsening due to the lack of specificity and spatiotemporal precision. In contrast, cardiac optogenetics relies on light sensitive ion channels stimulated to trigger excitation of cardiomyocytes solely making use of the inner cell mechanisms. This enables low-energy, non-damaging optical control of cardiac excitation with high resolution. Recently, the capability of optogenetic cardioversion was shown in Channelrhodopsin-2 (ChR2) transgenic mice. But these studies used mainly structured and local illumination for cardiac stimulation. In addition, since optogenetic and electrical stimulus work on different principles to control the electrical activity of cardiac tissue, a better understanding of the phenomena behind optogenetic cardioversion is still needed. The present study aims to investigate global illumination with regard to parameter characterization and its potential for cardioversion. Our results show that by tuning the light intensity without exceeding 1.10 mW mm-2, a single pulse in the range of 10-1,000 ms is sufficient to reliably reset the heart into sinus rhythm. The combination of our panoramic low-intensity photostimulation with optical mapping techniques visualized wave collision resulting in annihilation as well as propagation perturbations as mechanisms leading to optogenetic cardioversion, which seem to base on other processes than electrical defibrillation. This study contributes to the understanding of the roles played by epicardial illumination, pulse duration and light intensity in optogenetic cardioversion, which are the main variables influencing cardiac optogenetic control, highlighting the advantages and insights of global stimulation. Therefore, the presented results can be modules in the design of novel illumination technologies with specific energy requirements on the way toward tissue-protective defibrillation techniques.
心律失常期间观察到的复杂时空非线性与涡旋状兴奋波长和组织特征密切相关。因此，控制心律失常模式需要深入了解心律失常的发生与持续以及底物不稳定性之间的依赖关系。由于缺乏特异性和时空精确性，现有的治疗方法，如药物应用或高能电击，因潜在的副作用而导致预后恶化，这一点已被讨论。相比之下，心脏光遗传学依赖于光敏感离子通道，仅利用细胞内部机制来刺激触发心肌细胞的兴奋。这使得能够以低能量、无损伤的方式对心脏兴奋进行高分辨率的光学控制。最近，在通道视紫红质-2（ChR2）转基因小鼠中展示了光遗传学心脏复律的能力。但这些研究主要使用结构化和局部光照来刺激心脏。此外，由于光遗传学刺激和电刺激控制心脏组织电活动的原理不同，仍需要更好地理解光遗传学心脏复律背后的现象。本研究旨在研究全局光照的参数特征及其心脏复律的潜力。我们的结果表明，在不超过1.10 mW/mm²的情况下调节光强度，10 - 1000 ms范围内的单个脉冲足以可靠地使心脏恢复窦性心律。我们的全景低强度光刺激与光学标测技术相结合，可视化了波的碰撞，从而导致湮灭以及传播扰动，这些是导致光遗传学心脏复律的机制，其似乎基于与电除颤不同的过程。这项研究有助于理解心外膜光照、脉冲持续时间和光强度在光遗传学心脏复律中的作用，这些是影响心脏光遗传学控制的主要变量，突出了全局刺激的优势和见解。因此，所呈现的结果可作为设计具有特定能量要求的新型光照技术的模块，朝着组织保护除颤技术的方向发展。
