Auxetic Support Device for Chronic Myocardial Infarction

慢性心肌梗塞的拉胀支持装置

• 批准号: 9981420
• 负责人: Joseph Borrello
• 金额: $ 4.39万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9981420
• 关键词: Acute myocardial infarction; Address; Advisory Committees; American; Angiotensin-Converting Enzyme Inhibitors; Animal Model; Animals; Area; Biomechanics; Blood; Cardiac; Cardiac Output; Cardiovascular system; Chronic; Cicatrix; Cine Magnetic Resonance Imaging; Clinical; Clinical Research; Computer Models; Computer-Aided Design; Control Groups; Coronary; Device Designs; Devices; Diastole; Disease; Evaluation; Exposure to; Family suidae; Fellowship; Future; Geometry; Goals; Heart; Heart Diseases; Heart failure; High Performance Computing; Hour; Image; Imaging Techniques; In Vitro; Infarction; Intervention; Left; Left Ventricular Remodeling; Left ventricular structure; Magnetic Resonance Imaging; Measures; Mechanics; Meiosis; Modeling; Modification; Motion; Myocardial; Myocardial Infarction; Myocardium; Nature; Organ; Performance; Pharmacological Treatment; Physiological; Physiology; Pilot Projects; Procedures; Property; Psychological reinforcement; Pump; Radial; Recovery; Research; Research Personnel; Resolution; Stress; Stretching; Structure; Surgical sutures; Systole; Techniques; Testing; Therapeutic; Therapeutic Agents; Thick; Thinness; Time; Tissues; Training; Ventricular; Work; career; comorbidity; design; follow-up; heart function; heart imaging; implantable device; implantation; improved; in vitro Model; in vivo; innovation; materials science; mortality; multidisciplinary; new technology; novel; novel therapeutics; physical model; pre-doctoral; prototype; regenerative agent; response; simulation; success; training opportunity; usability; ventricular assist device

PROJECT SUMMARY Approximately every 40 seconds, someone will suffer a myocardial infarction (MI) in the US. While mortality due to acute MI has decreased over the past two decades, long-term consequences and comorbidities associated with chronic MI are increasing. In many cases, post-MI left ventricular (LV) remodeling manifests as progressive changes in LV structure and function. This remodeling initiates a degenerative cycle in which altered myocardial wall mechanics around the infarcted region cause the heart to mechanically compensate, resultantly placing still more strain on the infarct. Consequently, LV remodeling is the cause of approximately 70% of all heart failure (HF) cases, which kill approximately 100,000 Americans each year. Current treatments for chronic MI, HF, and LV remodeling include pharmacological treatments such as ACE-inhibitors and β- blockers, external mechanical ventricular assist devices (VADs), or invasive coronary revascularization procedures. These interventions are highly invasive and/or stopgap remedies, requiring continuous local modulation of the myocardial mechanics at the infarct. This proposal leverages auxetic materials, which counterintuitively get thicker rather than thin when stretched, to provide a means of restoring pumping function to the infarcted region of the heart. By fixing an auxetic ventricular support device (auxVSD) to the expanding, infarcted tissue, I plan to harness the energy currently wasted in the nonbeating infarct to instead stretch and expand an auxVSD, which would in turn stiffen and press against the myocardium, contributing to the ejection of blood during systole. Aim 1 will focus on the design, fabrication, and testing of potential auxetic structures and materials. Mechanical simulations will be used to identify auxetic structures that possess a favorable combination of displacement and force due to the auxetic effect. Concurrently, physical models will be fabricated for in vitro mechanical testing to inform the real-world feasibility of the simulations as well as provide preliminary information regarding the expected performance of an auxVSD in an in vivo animal model. In Aim 2 the efficacy of an auxVSD will be tested in an animal model of chronic MI and LV expansion to demonstrate its improvement of cardiac function through the dynamic modulation of myocardial mechanics in the infarcted region. Overall, this project design is both translational and highly-cross disciplinary in nature. Furthermore, improved understanding of the tissue- and organ-level changes associated with the onset and progression of MI will guide and validate this research through advanced cardiac imaging. These studies will not only provide a platform for rigorous multi-disciplinary integrated training in biomedical device design, mechanisms of cardiac disease, computational modeling, and translational imaging, but will also catapult a career that is focused on developing novel, technology-driven therapeutic strategies for cardiovascular and related diseases.

项目摘要 大约每40秒，有人会在美国遭受心肌梗塞（MI）。而死亡率 由于急性MI在过去的二十年中有所减少，因此长期后果和合并症 与慢性MI相关的人正在增加。在许多情况下，MI后左心室（LV）重塑表现为 LV结构和功能的进行性变化。这种重塑引发了一个退化循环，其中 梗塞区域周围的心肌壁机械改变导致心脏机械补偿， 显着在梗塞上增加了更多的压力。因此，LV重塑是大约的原因 所有心力衰竭（HF）病例的70％，每年杀死约100,000名美国人。当前治疗 对于慢性MI，HF和LV重塑包括药物治疗，例如ACE抑制剂和β- 阻滞剂，外部机械心室辅助设备（VADS）或侵入性冠状动脉血运重建 程序。这些干预措施是高度侵入性和/或停止疗法，需要持续的本地 在梗塞处的心肌力学调节。该提案利用辅助材料，这是 违反直觉在拉伸时变得更厚而不是薄，以提供一种恢复抽水功能的方法 到心脏梗塞区域。通过将辅助心室支撑装置（AUXVSD）固定到扩展 梗塞组织，我计划利用当前浪费在非饮食感染中的能量，而是伸展 扩展AUXVSD，这反过来会变硬并压在心肌上，导致弹射 收缩期间的血液。 AIM 1将专注于潜在辅助结构的设计，制造和测试 和材料。机械模拟将用于识别具有有利的辅助结构 由于辅助作用而导致的位移和力的组合。同时，物理模型将是 用于体外机械测试，以告知模拟的现实可行性，并提供 有关体内动物模型中AUXVSD的预期性能的初步信息。目标 2 AUXVSD的效率将在慢性MI和LV膨胀的动物模型中进行测试以证明 它通过梗塞中心肌力学的动态调节来改善心脏功能 地区。总体而言，这种项目设计本质上既是转化又高度交叉的纪律。此外， 对组织和器官级别的变化的了解得到了改善 MI将通过高级心脏成像指导和验证这项研究。这些研究不仅会提供 一个用于生物医学设备设计的严格多学科综合培训的平台，心脏机理 疾病，计算建模和翻译成像，但也将弹射着专注于 开发针对心血管和相关疾病的新型技术驱动理论策略。