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

基本信息

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
项目类别：
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

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

展开

项目摘要

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.

项目摘要冠心病是全球死亡的主要原因。用凝块破坏药物治疗患者（溶栓疗法）或动脉用导管（经皮冠状动脉介入）重新开放，但矛盾的是，恢复血液流向心肌会导致额外的伤害，从而限制这些程序。再灌注损伤似乎是一系列事件，由冠状动脉引发渗出（出血），最终无法恢复心肌灌注并导致细胞死亡在侵入周围区域的可行心肌细胞中。它可能是长期不良临床的预测指标结局或为心肌梗塞患者提供可治疗的靶标。成像方法再灌注损伤的分子机制特有了解这种疾病。我们假设铁是活性氧的产生的催化剂重复的心肌梗塞。我们提出了一系列实验，以研究铁和活性氧使用铁敏感的磁共振成像和正电子发射断层扫描。我们将用一系列病理学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技术。在AIM 1中，我们将调查使用MRI和PET的活性氧，铁和梗塞严重程度之间的关联。在AIM 2中，我们将确定再灌注损伤的成像标记与重塑的成像标记之间的关联程度受伤几周后离开心室。这项研究将使人们对时空关系有了新的了解在心肌梗死伤口愈合的亚急性和慢性时期的活性氧。这会导致对大型动物模型和人类的研究，这些模型和人类可以评估靶向成像生物标志物的疗法再灌注损伤。