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.

项目摘要 /摘要 这是为物理科学家马克·麦考利（Mark McCauley）博士提供的VA功绩奖研究赠款的申请 芝加哥Jesse Brown VA医疗中心的心脏病专家/电生理学家。该奖项将提供 McCauley博士提供了验证碳纳米管纤维（CNTF）为生物相容性所需的支持， 导电物质可以增强心脏的心室传导。为了实现这些目标， McCauley博士召集了一个电生理学家（Avitall博士和Razavi）和生物工程师（Drs。 Pasquali，Avitall和Perin）是该申请的顾问。 降低心肌传导速度（MCV）是致命心律不齐的重要促进者 包括单态性心室心动过速（VT）和猝死（SCD）。由于基础 传统的冠状动脉疾病风险因素以及与军事有关的暴露，例如PTSD和特工橙， 退伍军人更容易发展VT和SCD。以前，恢复本地心肌 由于缺乏结合强度，疲劳 - 电阻，电导率和电阻转移特性的低阻抗。最近，CNTF已描述 这些特性将这些特性结合成类似于缝合的材料。从我们的 实验室表明，CNTF能够在电子不同之间传输电荷 心肌区域，例如跨心疤痕和AV结。此外，CNTF是生物相容的 具有独特高电容，低阻抗材料/组织界面的材料。中心假设是 CNTF具有如此低的组织物质阻抗，以至于源 - 链接在电子之间的不匹配 分离的组织足够减小，以促进心脏组织内的跨心肌传导。测试 提出了这一假设，提出了三个具体目标：目标1 - 评估CNTF是否减少了源 - 链接不匹配 跨心疤痕； AIM 2 - 确定CNTF是否增加了跨障碍后心室疤痕的MCV 并防止VT；目标3 - 确定对长的导电稳定性，拉伸强度和炎症反应 cntf术语incrass。我们项目的创新是，我们第一次能够电桥接 用CNTF分离组织，以促进电信号的反式心肌转移。我们预期的结果 提出的目标的完成是对基于CNTF的基础机制的增强理解 电气传导以及CNTF将来应用所需的强临床前数据的发展 减少退伍军人中的不良心脏事件。