In Vivo Restoration of Myocardial Conduction with Carbon Nanotube Fibers

碳纳米管纤维体内心肌传导恢复

• 批准号: 10438661
• 负责人: Mark D McCauley
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10438661
• 关键词: Ablation; Acute; Age-Months; American; Animal Model; Anterior; Anti-Arrhythmia Agents; Area; Arrhythmia; Arteries; Award; Biocompatible Materials; Biomedical Engineering; Carbon Nanotubes; Cardiac; Cathodes; Cause of Death; Cessation of life; Charge; Chicago; Chronic; Cicatrix; Clinical Data; Coronary heart disease; Coupling; Data; Developed Countries; Development; Disease; Echocardiography; Electric Capacitance; Electric Conductivity; Electrodes; Electrophysiology (science); Event; Fatigue; Fiber; Functional disorder; Future; Goals; Healthcare Systems; Heart; Heart Diseases; Histology; Hospitalization; Impairment; Implant; Implantable Defibrillators; Infarction; Inflammatory Response; Laboratories; Left; Ligation; Maintenance; Measures; Mechanics; Medical center; Metals; Military Personnel; Mitochondria; Morbidity - disease rate; Mus; Muscle; Muscle Cells; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardium; Operative Surgical Procedures; Outcome; Physicians; Platinum; Polymers; Post-Traumatic Stress Disorders; Prevention; Property; Publishing; Radiofrequency Interstitial Ablation; Randomized; Rattus; Recovery; Research Priority; Research Project Grants; Research Proposals; Resistance; Risk; Risk Factors; Rodent; Scanning Electron Microscopy; Scientist; Serum; Sheep; Signal Transduction; Silk; Skeletal Muscle; Source; Spinal cord injury; Surface; Surgical Models; Surgical sutures; Tensile Strength; Testing; Therapeutic; Time; Tissues; United States Department of Veterans Affairs; Ventricular; Ventricular Fibrillation; Ventricular Tachycardia; Veterans; agent orange; base; biomaterial compatibility; cardiac implant; combat; electric impedance; flexibility; implantation; improved; in vivo; inflammatory marker; innovation; mortality; neonatal exposure; pre-clinical; prevent; restoration; sheep model; side effect; skeletal; sudden cardiac death; voltage

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.

项目概要/摘要 这是马克·麦考利 (Mark McCauley) 博士的 VA 优异奖研究补助金申请，他是一名医师兼科学家， 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 McCauley 博士获得了验证碳纳米管纤维 (CNTf) 作为生物相容性、 能够增强心脏心室传导的导电物质。为了实现这些目标， McCauley 博士组建了一支由电生理学家（Avitall 博士和 Razavi 博士）和生物工程师（Avitall 博士和 Razavi 博士）组成的团队。 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）。由于底层 传统的冠心病危险因素，以及与军事相关的暴露，如创伤后应激障碍（PTSD）和橙剂， 退伍军人更容易发生 VT 和 SCD。此前，原生心肌的恢复 由于缺乏结合强度、疲劳强度的生物相容性材料，传导一直是不可能的。 电阻、导电性和电荷转移特性的低阻抗。最近，CNTf被描述 将这些特性结合到制造的类似缝合线的材料中。我们的已发布数据和初步数据 实验室表明 CNTf 能够在电解剖学上不同的结构之间转移电荷 心肌区域，例如心室疤痕和房室交界处。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 具有如此低的组织材料阻抗，电解剖学上的源-汇不匹配 分离的组织被充分减少以促进心脏组织内的跨心肌传导。测试 根据这一假设，提出了三个具体目标： 目标 1 – 评估 CNTf 是否减少源-汇失配 穿过心室疤痕；目标 2 – 确定 CNTf 是否会增加穿过梗死后心室疤痕的 MCV 并预防VT；目标 3 – 确定长期传导的稳定性、拉伸强度和炎症反应 术语 CNTf 植入物。我们项目的创新之处在于，我们第一次能够以电力方式桥接 用 CNTf 分离组织，以促进电信号的跨心肌传输。我们的预期结果来自 完成所提出的目标是加深对基于 CNTf 的机制的理解 电传导，以及 CNTf 未来应用所需的强大临床前数据的开发 减少退伍军人的不良心脏事件。