Auxetic Ventricular Support Device for Chronic Myocardial Infarction

慢性心肌梗塞的拉胀心室支持装置

• 批准号: 9809489
• 负责人: KEVIN D COSTA
• 金额: $ 24.74万
• 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: 2019-08-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9809489
• 关键词: Acute myocardial infarction; American; Angiotensin-Converting Enzyme Inhibitors; Animal Model; Animals; Aortic Aneurysm; Applications Grants; Biomechanics; Blood; Cardiac; Cardiac Output; Chronic; Cicatrix; Cine Magnetic Resonance Imaging; Clinical; Clinical Research; Comorbidity; Computer Simulation; Computer-Aided Design; Congestive Heart Failure; Control Groups; Coronary; Data; Development; Device Designs; Devices; Diastole; Environment; Evaluation; Exposure to; Family suidae; Future; Geometry; Heart; Heart failure; Hiatal Hernia; High Performance Computing; Hour; Imaging Techniques; Impairment; In Vitro; Infarction; Intervention; Left; Left Ventricular Remodeling; Left ventricular structure; Magnetic Resonance Imaging; Measures; Mechanics; Meiosis; Modeling; Modification; Motion; Myocardial; Myocardial Infarction; Myocardium; National Institute of Biomedical Imaging and Bioengineering; Nature; Operative Surgical Procedures; Performance; Pharmaceutical Preparations; Pharmacological Treatment; Physiological; Pilot Projects; Preclinical Testing; Procedures; Property; Psychological reinforcement; Pump; Radial; Recovery; Research; Research Project Grants; Resolution; Safety; Stress; Stretching; Structure; Surgical sutures; Systole; Testing; Therapeutic Agents; Thick; Thinking; Time; Tissues; Ventricular; Work; design; efficacy testing; engineering design; follow-up; heart function; heart imaging; high risk; implantable device; implantation; improved; in vitro Model; in vivo; mechanical properties; mortality; multidisciplinary; novel; novel therapeutics; physical model; pre-clinical; prototype; regenerative agent; repaired; response; simulation; success; 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 can initiate a degenerative cycle in which altered myocardial wall mechanics around the infarcted region cause the heart to mechanically decompensate, resultantly placing still more strain on the infarct. Such adverse LV remodeling is the cause of approximately 70% of all heart failure (HF) cases, which kill approximately 100,000 Americans each year. Current therapies for chronic MI, HF, and LV remodeling include pharmacological treatments such as ACE-inhibitors and β- blockers, coronary revascularization procedures, patch-type ventricular support devices (VSD), and mechanical pump-type ventricular assist devices (VADs). However, drug interventions are stopgap remedies, while VADs are highly invasive and expensive, and VSDs do not contribute to ejection and can impair diastolic filling. This NIBIB R21 Exploratory/Developmental Research Grant proposal explores the potential for an unusual class of “auxetic” materials, which counterintuitively get thicker (rather than thinner) when stretched, to provide a novel means of passively restoring pumping function to the infarcted region of the heart. By fixing a patch-like auxetic ventricular support device (auxVSD) to the expanding infarcted tissue, we plan to harness the energy wasted on the non-beating infarct to instead stretch and expand an auxVSD, which would in turn stiffen and press against the infarct tissue, contributing to the ejection of blood during systole, while softening and allowing filling during diastole. Aim 1 will focus on the design, fabrication, and testing of potential auxetic structures and materials. Mechanical simulations will be used to identify and optimize auxetic structures in silico 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 the setting of a simplified cardiac tissue-like MRI phantom. In Aim 2 the efficacy of an auxVSD will be tested in a preclinical large animal model of chronic MI using displacement-sensitive DENSE MRI to evaluate its in vivo performance (vs. traditional VSD) for improving regional and global cardiac function through the dynamic modulation of cardiac mechanics in the infarct zone. The project design is both translational and highly cross- disciplinary. Despite the risky nature of this exploratory proposal, the assembled research team and environment are ideally suited to maximize the chances of successfully achieving the proposed aims, which would generate preliminary data for a future R01 that could evolve from this research, with the potential to transform current engineering design thinking as it relates to chronic myocardial infarction repair.

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。这种重塑可以启动一个退化循环，其中 梗塞区域周围心肌壁力学的改变导致心脏机械失代偿， 结果对梗塞部位施加了更大的压力。这种不良的 LV 重塑大约是 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。目前的疗法 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、冠状动脉血运重建手术、贴片型心室支持装置 (VSD) 和 机械泵型心室辅助装置（VAD）。然而，药物干预只是治标不治本， 而 VAD 具有高度侵入性且昂贵，而 VSD 不会促进射血并可能损害舒张压 填充。这项 NIBIB R21 探索性/发展性研究资助提案探讨了 不寻常的一类“拉胀”材料，在拉伸时会变得更厚（而不是更薄），这与直觉相反 提供了一种被动恢复心脏梗塞区域泵血功能的新方法。通过修复一个 我们计划利用贴片状拉胀心室支持装置（auxVSD）来扩大梗塞组织 浪费在非搏动梗塞上的能量来拉伸和扩大 auxVSD，这反过来又会 变硬并压在梗塞组织上，有助于收缩期血液的喷射，同时变软 并允许在舒张期充盈。目标 1 将重点关注潜在拉胀的设计、制造和测试 结构和材料。机械模拟将用于识别和优化拉胀结构 由于拉胀效应，硅片具有位移和力的良好组合。同时， 将制作用于体外机械测试的物理模型，以告知该技术在现实世界中的可行性 模拟，并提供有关 auxVSD 的预期性能的初步信息 简化的类似心脏组织的 MRI 模型的设置。在目标 2 中，将测试 auxVSD 的功效 使用位移敏感的 DENSE MRI 评估慢性 MI 的临床前大型动物模型的体内情况 通过动态改善局部和整体心脏功能（与传统 VSD 相比） 梗塞区心脏力学的调节。该项目设计既具有转化性又具有高度交叉性 纪律。尽管这一探索性提议具有风险性，但组建的研究团队和 环境非常适合最大限度地提高成功实现拟议目标的机会， 将为未来的 R01 生成初步数据，该数据可能会从这项研究中演变而来，并有可能 改变当前与慢性心肌梗塞修复相关的工程设计思维。