Ultrasound-mediated oxygen scavenging for inhibition of reperfusion injury

超声介导的氧清除抑制再灌注损伤

基本信息

批准号：
9319306
负责人：
Kevin Joseph Haworth
金额：
$ 15.85万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9319306
关键词：
Acoustics Active Learning Acute myocardial infarction Alpha Cell Animal Model Anterior Descending Coronary Artery Applications Grants Award Base Composition Basic Science Blood Blood Vessels Blood capillaries Blood flow Caliber Cardiac Myocytes Cardiac Volume Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Catheters Cell Culture Techniques Cell Death Cell Survival Cells Cessation of life Clinic Clinical Clinical Trials Coronary Data Development Diffuse Disease Distal Doctor of Philosophy Dose Emergency Situation Emulsions Ensure Event Feasibility Studies Fluorocarbons Free Radical Formation Free Radicals Future Gases Goals Heart Hemoglobin Human In Vitro Infarction Inflammatory Ischemia K-Series Research Career Programs Kinetics Knowledge Lead Left Life Ligation Liquid substance Measures Mechanical Stress Mediating Mentors Methods Microbubbles Modeling Modification Myocardial Infarction Myocardium New Zealand Oryctolagus cuniculus Outcome Oxidative Stress Oxygen Partial Pressure Patients Phase Transition Physics Physiologic pulse Physiological Plasma Positioning Attribute Preparation Principal Investigator Procedures Process Production Reactive Oxygen Species Reperfusion Injury Reperfusion Therapy Research Research Training Risk Saline Savings Scientist Series Source Stress System Techniques Testing Therapeutic Embolization Tissue Viability Tissues Training Training Technics Translating Translational Research Translations Treatment Efficacy Ultrasonography United States National Institutes of Health Whole Blood Work animal model selection base capillary cytokine design experimental study heart cell hemodynamics improved in vivo model design novel novel strategies novel therapeutics oxygen transport percutaneous coronary intervention programs signal processing skills vapor vaporization

项目摘要

PROJECT SUMMARY/ABSTRACT Myocardial infarction is induced by an ischemic event and often leads to damage of the myocardium and potentially death. The primary clinical goal during treatment of myocardial infarction is to restore blood flow to the myocardium as quickly as possible. However, paradoxically, the reperfusion can cause significant damage to the myocardium. Of the total infarcted volume, potentially up to 50% can be attributed to reperfusion and not ischemia. The reperfusion injury occurs, in part, due to the ischemic tissue converting the newfound supply of oxygen into reactive oxygen species. Reactive oxygen species can significantly damage a cell and lead to cell death. This career development award (CDA) takes advantage of the principal investigator's quantitative background in ultrasound physics, signal processing, and cavitation to develop a novel approach to inhibiting reperfusion injury. The technique relies on a process known as acoustic droplet vaporization, where a liquid droplet is phase-transitioned into a gas microbubble when exposed to ultrasound. The microbubble acts a sink for dissolved oxygen in whole blood, effectively sequestering the oxygen within the microbubble so that the oxygen cannot diffuse into the tissue. Our central hypothesis is that ultrasound-mediated oxygen scavenging during reperfusion, following an ischemic event, increases cell and tissue viability. This hypothesis will be tested through studies focusing on the efficiency and efficacy of oxygen scavenging in vitro, ex vivo, and in vivo. The first aim of this CDA is to understand how the efficiency of oxygen scavenging varies based the composition of the droplets. Next, a series of experiments will be performed to measure the reactive oxygen species production and cell death in cell culture, isolated whole heart with Langendorff preparation, and finally in vivo. The progression of these experiments will ensure a thorough understanding of the therapy and how modifications to the approach can be made to improve therapeutic efficacy. In the process of carrying out these aims, the PI will undergo mentored research training to develop skills that will enable the PI to take future basic science discoveries in ultrasound physics and advance them towards cardiovascular application in humans. In particular, the PI will develop a working expertise of oxygen transport, cardiovascular physiology, ischemia-reperfusion injury, the selection, implementation, and analysis of relevant animal models, and the design of translatable ultrasound systems. Didactic coursework, independent study, and hands-on experiential learning will form the bulk of the training techniques used. The CDA has been carefully designed to supplement the PI's extensive quantitative background to enable him to successfully build an independent research program focused on the treatment of cardiovascular diseases.

项目概要/摘要心肌梗塞是由缺血事件引起的，通常会导致心肌和心肌的损伤。潜在的死亡。心肌梗塞治疗的主要临床目标是恢复心肌梗死的血流。尽快心肌。然而，矛盾的是，再灌注会造成严重损害到心肌。在总梗塞体积中，可能高达 50% 是由于再灌注和不是缺血。再灌注损伤的发生部分是由于缺血组织转换了新发现的供应将氧气转化为活性氧。活性氧会严重损害细胞并导致细胞死亡。该职业发展奖（CDA）利用了首席研究员的定量超声波物理学、信号处理和空穴的背景，开发一种新的抑制方法再灌注损伤。该技术依赖于一种称为声学液滴汽化的过程，其中液体当暴露于超声波时，液滴相变成气体微泡。微气泡起到水槽的作用针对全血中的溶解氧，有效地将氧气隔离在微泡内，使氧气不能扩散到组织中。我们的中心假设是超声波介导的除氧作用在缺血事件后的再灌注期间，增加细胞和组织的活力。这个假设将是通过专注于体外、离体和体内除氧效率和功效的研究进行测试体内。该 CDA 的首要目标是了解除氧效率如何随条件变化液滴的组成。接下来，将进行一系列实验来测量活性氧细胞培养中的物种产生和细胞死亡，用 Langendorff 制剂分离整个心脏，最后体内。这些实验的进展将确保彻底了解该疗法以及如何可以对该方法进行修改以提高治疗效果。在执行过程中为了实现这些目标，PI 将接受指导性研究培训，以培养技能，使 PI 能够在未来超声物理学的基础科学发现并将其推向心血管应用人类。特别是，PI 将培养氧气输送、心血管生理学、缺血再灌注损伤相关动物模型的选择、实施和分析以及可平移超声系统的设计。教学课程、独立学习和实践体验学习将构成所使用的培训技术的大部分。 CDA 经过精心设计，补充PI广泛的定量背景，使他能够成功建立一个独立的研究计划的重点是心血管疾病的治疗。