Research Group Biomedical Physics, Max Planck Institute for Dynamics and Self-Organization; Research Electronics Department, Max Planck Institute for Dynamics and Self-Organization.
Research Group Biomedical Physics, Max Planck Institute for Dynamics and Self-Organization.
J Vis Exp. 2021 Aug 26(174). doi: 10.3791/62335.
Ventricular tachyarrhythmias are a major cause of mortality and morbidity worldwide. Electrical defibrillation using high-energy electric shocks is currently the only treatment for life-threatening ventricular fibrillation. However, defibrillation may have side-effects, including intolerable pain, tissue damage, and worsening of prognosis, indicating a significant medical need for the development of more gentle cardiac rhythm management strategies. Besides energy-reducing electrical approaches, cardiac optogenetics was introduced as a powerful tool to influence cardiac activity using light-sensitive membrane ion channels and light pulses. In the present study, a robust and valid method for successful photostimulation of Langendorff perfused intact murine hearts will be described based on multi-site pacing applying a 3 x 3 array of micro light-emitting diodes (micro-LED). Simultaneous optical mapping of epicardial membrane voltage waves allows the investigation of the effects of region-specific stimulation and evaluates the newly induced cardiac activity directly on-site. The obtained results show that the efficacy of defibrillation is strongly dependent on the parameters chosen for photostimulation during a cardiac arrhythmia. It will be demonstrated that the illuminated area of the heart plays a crucial role for termination success as well as how the targeted control of cardiac activity during illumination for modifying arrhythmia patterns can be achieved. In summary, this technique provides a possibility to optimize the on-site mechanism manipulation on the way to real-time feedback control of cardiac rhythm and, regarding the region specificity, new approaches in reducing the potential harm to the cardiac system compared to the usage of non-specific electrical shock applications.
室性心动过速是全球范围内导致死亡率和发病率的主要原因。目前，使用高能电击进行电除颤是治疗危及生命的心室颤动的唯一方法。然而，除颤可能有副作用，包括难以忍受的疼痛、组织损伤和预后恶化，这表明需要开发更温和的心脏节律管理策略来满足重大的医疗需求。除了降低能量的电方法外，心脏光遗传学已被引入作为一种使用光敏感膜离子通道和光脉冲来影响心脏活动的强大工具。在本研究中，将描述一种基于多点起搏的稳健有效的方法，该方法使用 3 x 3 微发光二极管 (micro-LED) 阵列进行多部位起搏，从而成功地对 Langendorff 灌注完整的鼠心进行光刺激。心外膜膜电压波的同时光学映射允许研究区域特异性刺激的效果，并直接在现场评估新诱导的心脏活动。所得结果表明，除颤的效果强烈依赖于心律失常期间选择的光刺激参数。将证明心脏的照明区域对于终止成功以及如何通过在照明期间对心脏活动进行有针对性的控制来改变心律失常模式起着至关重要的作用。总之，该技术提供了一种优化现场机制操作的可能性，以便实现心脏节律的实时反馈控制，并且在区域特异性方面，与非特异性电冲击应用相比，该技术为减少对心脏系统的潜在危害提供了新的方法。
