In Vivo Restoration of Myocardial Conduction with Carbon Nanotube Fibers

项目总结/摘要 这是一份为马克·麦考利博士申请退伍军人管理局优秀奖研究补助金的申请，他是一名医生兼科学家， 芝加哥杰西布朗退伍军人医疗中心的心脏病专家/电生理学家。该奖项将提供 博士麦考利与必要的支持，以验证碳纳米管纤维（CNTf）作为一种生物相容性， 能够增强心室传导的导电物质。为了实现这些目标， 博士麦考利组建了一个由电生理学家（Avitall博士和Razavi博士）和生物工程师（Dr. Pasquali、Avitall和Perin），他们是本申请的顾问。 心肌传导速度（MCV）降低是致命性心律失常的重要原因 包括单形性室性心动过速（VT）和心源性猝死（SCD）。由于潜在 传统的冠状动脉疾病风险因素，以及与军事有关的暴露，如创伤后应激障碍和橙子剂， 退伍军人更容易发展VT和SCD。以前，天然心肌的恢复 由于缺乏结合了强度、疲劳 电阻、导电性和对电荷转移特性的低阻抗。最近，CNTf已经被描述为 将这些特性结合到一种类似缝合线的材料中。我们的已发布和初步数据 实验室表明CNTf能够在电解剖学上不同 心肌区域，如心室瘢痕和房室交界处。此外，CNTf具有生物相容性， 具有独特的高电容、低阻抗材料/组织界面的材料。中心假设是 CNTf具有如此低的组织-材料阻抗， 分离的组织被充分地减小以促进心脏组织内的跨心肌传导。测试 基于这一假设，本文提出了三个具体目标：目标1 -评估CNTf是否减少了源-汇失配 目的2 -确定CNTf是否增加梗死后心室瘢痕的MCV 目的3 -确定传导稳定性、抗张强度和对长- 术语CNTf植入物。我们项目的创新之处在于，我们第一次能够用电力连接 用CNTf分离组织，以促进电信号的跨心肌传输。我们的预期结果 完成拟议的目标是加深对基于CNTf的机制的理解 电传导，以及CNTf未来应用所需的强有力的临床前数据的开发 减少退伍军人的不良心脏事件。

Project Summary / Abstract This is an application for a VA Merit Award Research Grant for Dr. Mark McCauley, a physician-scientist and staff Cardiologist/Electrophysiologist at the Jesse Brown VA Medical Center in Chicago. This award will provide Dr. McCauley with the support necessary to validate carbon nanotube fibers (CNTf) as a biocompatible, electrically conductive substance able to enhance ventricular conduction in the heart. To achieve these goals, Dr. McCauley has assembled a team of Electrophysiologists (Drs. Avitall and Razavi) and Bioengineers (Drs. Pasquali, Avitall, and Perin), who are Consultants on this application. Reduced myocardial conduction velocity (MCV) is a significant contributor to lethal cardiac arrhythmias including monomorphic ventricular tachycardia (VT) and sudden cardiac death (SCD). Due to underlying traditional coronary disease risk factors, and military-related exposures such as PTSD and agent orange, Veterans are more susceptible to developing VT and SCD. Previously, restoration of native myocardial conduction has not been possible because of lack of a biocompatible material that combines strength, fatigue- resistance, conductibility, and low impedance to charge transfer properties. Recently, CNTf have been described that combine these properties into a manufactured suture-like material. Published and preliminary data from our laboratory suggest that CNTf are capable of transferring electrical charge between electroanatomically distinct areas of myocardium, such as across ventricular scar and the AV junction. Additionally, CNTf are biocompatible materials with a unique high capacitance, low impedance material/tissue interface. The central hypothesis is that CNTf have such a low tissue-material impedance, that source-sink mismatch between electroanatomically separated tissues is sufficiently reduced to facilitate trans-myocardial conduction within cardiac tissue. To test this hypothesis, three Specific Aims are proposed: Aim 1 – Assess whether CNTf reduce source-sink mismatch across ventricular scar; Aim 2 – Determine whether CNTf increase MCV across post-infarction ventricular scar and prevent VT; Aim 3 – Determine the conductive stability, tensile strength, and inflammatory response to long- term CNTf implants. The innovation of our project is that for the first time, we are able to bridge electrically separate tissues with CNTf to facilitate trans-myocardial transfer of electrical signal. Our expected outcome from completion of the proposed Aims is an enhanced understanding of the mechanisms underlying CNTf-based electrical conduction, and the development of strong pre-clinical data necessary for the future application of CNTf to reduce adverse cardiac events in Veterans.