Optical Mapping of Cardiac Electromechanics in the In Vivo Setting

心脏收缩是由电去极化波触发的， 心肌光学映射是一种基于荧光的技术，用于跟踪电波的移动 刺穿心脏相对于基于电极的技术，其有利之处在于其对跨膜细胞成像。 电位，而不是细胞外电位，因此提供了电恢复的信息， 是许多危险心律失常的关键因素。它通常还具有比电学更高的空间分辨率。 映射并且不受强电刺激的不利影响。由于这些优点，光学 标测已经成为实验心脏电生理学研究的支柱。但传统 光学标测具有主要缺点：由于心脏运动引起的伪影， 离体心脏，其中收缩被抑制。这已经排除了它在临床上的使用， 体内动物制剂。它也限制了光学测绘的应用，纯粹的电生理 问题-心脏病学的重要问题，涉及心脏中的双向机电相互作用， 当机械功能被消除时，心脏不能被处理。 最近引入了一种新的方法来消除这种限制， 的运动跟踪和多波长的激励，以执行光学标测在离体跳动的心脏。这 方法同时跟踪电传播和量化心肌的变形， 收缩或加载。因此，它可以用于心脏生理学中的一系列新问题，这些问题不能被 利用传统的光学映射或其它技术直接寻址。然而，该方法仍然具有 由离体制备施加的限制，例如，过于简单的机械负载条件 应用于心脏;自主神经支配的影响;和有限的氧气携带能力， 晶体溶液，这可能会影响心脏的代谢状态。 为了解决这些局限性，本项目将采取下一步措施，实施体内光学标测： 目的1：设计一种用于体内、开胸、大型动物的光机电标测方法 准备工作心外膜运动跟踪和激励比率是该方法的关键组成部分。 目的2：验证新方法产生的机电测量值，并表征任何 生理副作用 这些目标的成功实现将为心脏病学研究提供一种新的工具。一些潜在 应用包括：临床前评估治疗的机械功效和电气安全性， 缺血性心脏病;室壁伸展对正常增殖和 研究机械载荷条件对电传播的影响; 研究多部位起搏方案对局部室壁运动的影响。

Heart contraction is triggered by a wave of electrical depolarization that propagates through the myocardium. Optical mapping is a fluorescence-based technology for tracking electrical waves as they move through the heart. It is advantageous relative to electrode-based technology in that it images transmembrane potential, rather than extracellular potential, and therefore provides information on electrical recovery, which is a key factor in many dangerous arrhythmias. It also typically has higher spatial resolution than electrical mapping and is not adversely affected by strong electrical stimuli. Because of these advantages, optical mapping has become a mainstay of experimental cardiac electrophysiology research. However, traditional optical mapping has a major disadvantage: because of artifacts caused by cardiac motion, it is typically used in ex vivo hearts in which contraction is pharmacologically arrested. This has precluded its use clinically and in in vivo animal preparations. It has also limited optical mapping’s application to purely electrophysiological questions—important questions in cardiology that involve the bidirectional electromechanical interactions in the heart cannot be addressed when mechanical function has been abolished. Some of this limitation was recently removed by the introduction of a novel method that uses a combination of motion tracking and multi-wavelength excitation to perform optical mapping in isolated beating hearts. This method simultaneously tracks electrical propagation and quantifies deformation of the myocardium due to contraction or loading. It can therefore be used for a new set of questions in cardiac physiology that cannot be directly addressed with traditional optical mapping or other technologies. However, the method still has limitations imposed by the ex vivo preparation, for example, the overly-simple mechanical loading conditions applied to the heart; the effects of autonomic denervation; and the limited oxygen carrying capacity of crystalloid solution, which may affect the heart’s metabolic state. To address these limitations, this project will take the next step and implement in vivo optical mapping: Aim 1: Engineer an optical electromechanical mapping method for use in in vivo, open-chest, large animal preparations. Epicardial motion tracking and excitation ratiometry are key components of the method. Aim 2: Validate the electromechanical measurements generated by the new method and characterize any physiological side effects. Successful completion of these aims will result in a new tool for cardiology research. A few potential applications include: preclinical evaluation of the mechanical efficacy and electrical safety of therapies for ischemic heart disease; investigation of the effects of wall stretch on normal propagation and arrhythmogenesis; investigation of the effects of mechanical loading conditions on electrical propagation; and investigation of the effects of multi-site pacing protocols on regional wall motion.