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.

项目总结