Optical Mapping of Cardiac Electromechanics in the In Vivo Setting

心脏收缩是由电除极波引发的，它通过心脏 心肌。光学测绘是一种基于荧光的技术，用于跟踪移动的电波 穿过心脏。与基于电极的技术相比，它的优势在于它能成像跨膜 电位，而不是细胞外电位，因此提供了关于电恢复的信息，这是 是许多危险的心律失常的关键因素。它的空间分辨率通常也高于电子设备。 测绘，不会受到强烈的电刺激的不利影响。由于这些优势，光学 标测已成为实验性心脏电生理学研究的支柱。然而，传统的 光学映射有一个主要缺点：由于心脏运动引起的伪影，它通常用于 体外心脏的收缩在药物上被阻止。这就排除了它在临床和临床中的使用。 活体动物制剂。它还将光学标测的应用局限于纯粹的电生理 问题-心脏病学中涉及双向机电相互作用的重要问题 当机械功能被取消时，心脏就不能被处理了。 最近，通过引入一种新的方法来消除这种限制，该方法使用了 运动跟踪和多波长激发相结合，在孤立跳动的心脏中执行光学标测。这 方法同时跟踪电传播并量化由于 收缩或加载。因此，它可以用于心脏生理学中一组新的问题，这些问题不能 用传统的光学测绘或其他技术直接寻址。然而，该方法仍然具有 体外制剂施加的限制，例如过于简单的机械加载条件 应用于心脏；自主神经失神经的影响；以及有限的携氧能力 晶体溶液，这可能会影响心脏的代谢状态。 为了解决这些限制，该项目将进入下一步，实现体内光学映射： 目的1：设计一种用于活体、开胸、大型动物的光机电标测方法 准备工作。心外膜运动跟踪和兴奋率测量是该方法的关键组成部分。 目标2：验证新方法产生的机电测量，并表征任何 生理副作用。 这些目标的成功完成将为心脏病学研究带来新的工具。有几个潜力 应用包括：治疗的机械疗效和电气安全性的临床前评估 缺血性心脏病；室壁牵拉对正常繁殖和 心律失常的发生；机械负荷条件对电传播的影响的调查；以及 多部位起搏对节段性室壁运动影响的研究。

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.