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.

项目概要 冠心病是全世界死亡的主要原因。患者接受溶栓药物治疗 （溶栓治疗）或用导管重新打开动脉（经皮冠状动脉介入治疗），但是， 矛盾的是，恢复心肌血流可能会导致额外的损伤，从而限制了治疗的成功 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），最终导致心肌灌注无法恢复并导致细胞死亡 梗死周围区域的存活心肌细胞。它可能是长期不良临床的预测因子 结局或为心肌梗死患者提供可修改的治疗目标。成像方法 针对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。我们假设铁是活性氧产生的催化剂 再灌注心肌梗塞。我们提出了一系列实验来研究之间的关联 使用铁敏感磁共振成像和正电子发射来检测铁和活性氧 断层扫描。我们将通过一系列病理学来验证这些体内非侵入性成像方式， 大型动物模型中的免疫组织化学和光谱测定技术。在目标 1 中，我们将调查 使用 MRI 和 PET 研究活性氧、铁和梗塞严重程度之间的关联。在目标 2 中，我们 将确定再灌注损伤的成像标记物与脑组织重塑之间的关联程度 受伤几周后的左心室。这项研究将对时空关系产生新的认识。 活性氧在心肌梗死伤口愈合的亚急性和慢性期。这将 导致对大型动物模型和人类的研究可以评估针对成像生物标志物的治疗 再灌注损伤。