Non-invasive imaging of reactive oxygen species in reperfusion injury myocardial infarction

再灌注损伤心肌梗死中活性氧的无创成像

• 批准号: 10716836
• 负责人: PACO E. BRAVO
• 金额: $ 77.03万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10716836
• 关键词: Acute myocardial infarction; Affect; Animal Model; Animals; Anterior Descending Coronary Artery; Arrhythmia; Arteries; Biological Assay; Blood flow; Cardiac; Cardiac Myocytes; Cardiovascular system; Catheters; Cause of Death; Cell Death; Chronic; Clinical; Coagulation Process; Complication; Computed Tomography Scanners; Coronary artery; Coronary heart disease; Data; Deposition; Development; Diagnosis; Discipline of Nuclear Medicine; Disease; EFRAC; Edema; Erythrocytes; Event; Extravasation; Failure; Family suidae; Fibrosis; Fluorine; Glutathione; Goals; Heart; Heart failure; Hemorrhage; High Prevalence; Human; Image; Imaging Techniques; Immunohistochemistry; Impairment; Infarction; Injury; Intervention; Iron; Iron-Binding Proteins; Ischemia; Label; Left; Left Ventricular Function; Left Ventricular Mass; Left Ventricular Remodeling; Lipid Peroxidation; Macrophage; Magnetic Resonance Imaging; Maps; Measures; Methods; Molecular; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardial perfusion; Myocardium; Outcome; Pathology; Patients; Pharmaceutical Preparations; Physicians; Positron-Emission Tomography; Procedures; Production; Proteins; Reactive Oxygen Species; Reperfusion Injury; Reperfusion Therapy; Research Personnel; Risk; Rubidium; Series; Severities; Specificity; Spectrometry; Structure; Surgeon; System; Techniques; Testing; Therapeutic; Thick; Thrombolytic Therapy; Validation; Ventricular; Ventricular Remodeling; analog; cardiac magnetic resonance imaging; catalyst; cell injury; clinical care; dihydroethidium; experience; experimental study; fluorescence imaging; heart imaging; hemodynamics; high risk; imaging biomarker; imaging modality; improved; in vivo; in vivo imaging; method development; myocardial injury; non-invasive imaging; novel; patient prognosis; percutaneous coronary intervention; prognostic value; restoration; spatiotemporal; standard care; success; targeted treatment; tool; translational goal; uptake; wound healing

Project Summary Coronary heart disease is the leading cause of death worldwide. Patients are treated with clot-busting drugs (thrombolytic therapy) or the artery is reopened with a catheter (percutaneous coronary intervention), but, paradoxically, restoration of blood flow to the heart muscle can cause additional injury that limits the success of these procedures. Reperfusion injury appears to be a cascade of events, initiated by coronary artery extravasation (hemorrhage), culminating in a failure to restore myocardial perfusion and leading to cell death among viable cardiomyocytes in the peri-infarct region. It may be a predictor of long-term adverse clinical outcomes or provide a therapy-modifiable target in patients with myocardial infarction. Imaging methods specific to the molecular mechanisms of reperfusion injury would improve clinical care and our scientific understanding of this disease. We hypothesize that iron is a catalyst for reactive oxygen species production in reperfused myocardial infarction. We propose a series of experiments to investigate the association between iron and reactive oxygen species using iron-sensitive magnetic resonance imaging and positron emission tomography. We will validate these in vivo non-invasive imaging modalities with a battery of pathology, immunohistochemistry, and spectrometry techniques in a large animal model. In Aim 1, we will investigate the association between reactive oxygen species, iron and severity of infarction using MRI and PET. In Aim 2, we will determine the extent of association between imaging markers of reperfusion injury and remodeling of the left ventricle weeks after injury. This study will give a new understanding of the spatiotemporal relationships of reactive oxygen species in the sub-acute and chronic period of myocardial infarction wound healing. This will lead to studies in large animal models and humans that can evaluate therapies targeting imaging biomarkers of reperfusion injury.

项目摘要 冠心病是世界范围内主要的死亡原因。病人用溶栓药物治疗。 (溶栓治疗)或用导管重新开放动脉(经皮冠状动脉介入治疗)，但是， 矛盾的是，心肌血流量的恢复可能会造成额外的损伤，从而限制介入治疗的成功 这些程序。再灌注损伤似乎是由冠状动脉引发的一系列事件。 外渗(出血)，最终导致无法恢复心肌灌注并导致细胞死亡 在梗死区周围存活的心肌细胞中。它可能是临床长期不良反应的预测因子。 或为心肌梗死患者提供治疗可修改的靶点。成像方法 明确再灌注损伤的分子机制将改善临床护理和我们的科学 对这种疾病的了解。我们假设铁是产生活性氧物种的催化剂。 再灌注性心肌梗死。我们提出了一系列实验来研究两者之间的联系 用铁敏感磁共振成像和正电子发射研究铁和活性氧物种 体层摄影术。我们将用一组病理学来验证这些体内非侵入性成像方式， 在一个大型动物模型中的免疫组织化学和光谱技术。在目标1中，我们将调查 磁共振成像和正电子发射计算机断层扫描分析脑梗塞严重程度与活性氧、铁的关系。在目标2中，我们 将确定再灌注损伤的影像标志物与血管重塑之间的关联程度。 损伤后数周的左心室。这项研究将给我们一个新的理解。 亚急性期和慢性期心肌梗死创面愈合过程中的氧自由基。这将是 在大型动物模型和人类中进行研究，评估靶向成像生物标记物的治疗方法 再灌注损伤。