In Vivo Restoration of Myocardial Conduction with Carbon Nanotube Fibers

项目摘要/摘要 这是一份为马克·麦考利博士申请退伍军人荣誉奖研究补助金的申请，他是一名内科科学家和 芝加哥杰西·布朗退伍军人医学中心的心脏病专家/电生理学家。该奖项将提供 McCauley博士拥有验证碳纳米管纤维(CNTF)作为生物相容性所必需的支持， 能够增强心脏中的心室传导的导电物质。为了实现这些目标， 麦考利博士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.Razavi博士)组成的团队。 Pasqui、Avitall和Perin)，他们是此应用程序的顾问。 心肌传导速度减慢是致命性心律失常的重要因素。 包括单形性室性心动过速(VT)和心脏性猝死(SCD)。由于潜在的 传统的冠心病风险因素，以及与军事相关的暴露，如创伤后应激障碍和橙剂， 退伍军人更容易发生室上性心动过速和SCD。以前，自然心肌的恢复 由于缺乏一种结合强度、疲劳的生物兼容材料，传导一直是不可能的。 电阻、导电性和低阻抗至电荷转移特性。最近，CNTF被描述为 将这些特性结合到一种人造缝合线状材料中。来自我们的已公布数据和初步数据 实验室研究表明，CNTF能够在不同解剖结构之间转移电荷 心肌区，如横跨室壁疤痕和房室交界处。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具有如此低组织材料阻抗，在电子解剖学上 分离的组织被充分减少，以促进心脏组织内的跨心肌传导。为了测试 在这一假设下，提出了三个具体的目标：目标1-评估CNTF是否减少了源-汇失配 跨越脑室疤痕；目标2：确定CNTF是否增加了跨脑梗塞后脑室疤痕的MCV 和预防室性心动过速；目标3-测定长期和长期的传导稳定性、抗拉强度和炎症反应。 术语CNTF植入物。我们项目的创新之处在于，我们第一次能够使用电桥 用CNTF分离组织，以促进电信号的跨心肌传递。我们的预期结果来自 拟议目标的完成是对基于CNTF的基础机制的更好理解 电传导，以及未来CNTF应用所需的强大临床前数据的开发 以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.