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.

项目概要 在美国，大约每 40 秒就会有人罹患心肌梗塞 (MI)。虽然死亡率 由于急性心梗在过去二十年中有所减少，长期后果和合并症 与慢性心肌梗死相关的疾病正在增加。在许多情况下，MI后左心室（LV）重构表现为 左心室结构和功能的渐进性变化。这种重塑启动了一个退化循环，其中 梗塞区域周围心肌壁力学的改变导致心脏机械补偿， 结果对梗塞部位施加了更大的压力。因此，左心室重塑大约是导致 占所有心力​​衰竭 (HF) 病例的 70%，每年约有 100,000 名美国人因此死亡。目前的治疗方法 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、体外机械心室辅助装置 (VAD) 或侵入性冠状动脉血运重建术 程序。这些干预措施是高度侵入性和/或权宜之计，需要持续的局部治疗 梗塞处心肌力学的调节。该提案利用了拉胀材料， 与直觉相反，拉伸时会变得更厚而不是更薄，以提供恢复泵送功能的方法 到心脏的梗塞区域。通过将拉胀心室支持装置 (auxVSD) 固定到扩张的、 梗塞组织，我计划利用当前在非搏动梗塞中浪费的能量来拉伸和 扩大 auxVSD，这反过来会变硬并压迫心肌，从而促进射血 收缩期间的血液。目标 1 将重点关注潜在拉胀结构的设计、制造和测试 和材料。机械模拟将用于识别具有有利的拉胀结构 由于拉胀效应而产生的位移和力的组合。同时，物理模型将 为体外机械测试而制造，以告知模拟的现实可行性并提供 有关 auxVSD 在体内动物模型中的预期性能的初步信息。瞄准 2 auxVSD 的功效将在慢性 MI 和 LV 扩张的动物模型中进行测试，以证明 通过动态调节梗塞心肌力学来改善心脏功能 地区。总体而言，该项目设计本质上是转化性的和高度跨学科的。此外， 更好地了解与疾病的发作和进展相关的组织和器官水平的变化 MI 将通过先进的心脏成像来指导和验证这项研究。这些研究不仅将提供 生物医学设备设计、心脏机制等领域严格的多学科综合培训平台 疾病、计算建模和转化成像，但也将推动专注于以下领域的职业生涯 为心血管及相关疾病开发新颖的、技术驱动的治疗策略。