In-vivo Imaging of Calcium in the Heart

心脏钙的体内成像

基本信息

批准号：
7793533
负责人：
Barry London
金额：
$ 22.73万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7793533
关键词：
Acute Animals Anterior Descending Coronary Artery Area Arrhythmia Autonomic nervous system CMV promoter Calcium Canis familiaris Cardiac Cardiac Myocytes Cell physiology Cells Cessation of life Chest Chronic Data Dependovirus Development Diagnostic Disease Engineering Fiber Optics Fluorescent Dyes Functional disorder Heart Heart Diseases Heart failure Heterogeneity Homeostasis Image Imaging technology Implant In Situ In Vitro Ions Ischemia Knowledge Left Life Ligation Light Link Location London Maps Measurement Measures Methods Modality Modeling Myocardial Myocardial Infarction Optics Organ Oryctolagus cuniculus Pathology Physiological Play Preparation Proteins Regulation Reperfusion Therapy Reporting Role RyR2 Ryanodine Receptor Calcium Release Channel Ryanodine Receptors SERCA2a Sarcoplasmic Reticulum Serotyping Signal Transduction Site Stress Sudden Death Surface System Techniques Technology Testing United States Variant Ventricular Ventricular Dysfunction awake base heart cell high risk improved in vivo insight nerve supply novel novel therapeutics optical fiber phospholamban premature pressure public health relevance reuptake rhod-2 voltage

项目摘要

DESCRIPTION (provided by applicant): Calcium (Ca2+) oscillations underlie many important cellular processes that enable organ function, including contraction in the heart. Abnormalities in Ca2+ handling accompany most types of cardiac pathology, and may contribute to both ventricular dysfunction and arrhythmias. This proposal is aimed at developing a novel imaging technology to study spatial and temporal heterogeneities in Ca2+ transients in living animals. We will use adeno-associated virus serotype 9 (AAV-9) to stably deliver GCaMP2, a recently developed genetically encoded Ca2+-sensing molecule, into the hearts of living animals. Fiber optical probes (optrodes) will then be used to serially assess Ca2+ concentration at multiple transmural sites in both open- and closed-chest animals. We will test the hypothesis that transmural variation in Ca2+ transients during pathological states contributes to the development of cardiac dysfunction and arrhythmias. In Specific Aim 1, acute changes in Ca2+ transients will be studied in an open-chest rabbit model of ischemia-reperfusion during ligation of the left anterior descending coronary artery. In Specific Aim 2, chronic changes in Ca2+ transients will be studied in dogs with pacing-induced heart failure. These temporal and spatial measurements of in-situ Ca2+ transients at multiple sites in the heart will provide insights into the mechanisms by which abnormal Ca2+ handling contributes to cardiac dysfunction and arrhythmias in the setting of ischemia and heart failure. PUBLIC HEALTH RELEVANCE: Heart attacks and heart failure remain leading causes of illness and premature death in the United States. Calcium triggers the contraction during each heart beat, and calcium regulation is abnormal after a heart attack and in heart failure. In this proposal, we will develop a method to measure calcium concentrations in the heart cells of living animals and use this technology to better understand how abnormalities in calcium contribute to heart failure and sudden death.

描述（由申请人提供）：钙（CA2+）振荡是许多重要的细胞过程，这些过程可以使器官功能，包括心脏的收缩。 CA2+处理的异常伴随着大多数类型的心脏病理，并且可能导致心室功能障碍和心律不齐。该建议旨在开发一种新型的成像技术来研究活动物中Ca2+瞬态的空间和时间异质性。我们将使用腺相关的病毒血清型9（AAV-9）稳定地传递GCAMP2，这是一种最近开发的遗传编码的Ca2+传感分子，进入活物的心脏。然后，光纤探针（OPTRODES）将用于评估开放式和闭孔动物多个透壁位点的Ca2+浓度。我们将检验以下假设：病理状态期间Ca2+瞬态的透壁差异有助于心脏功能障碍和心律不齐的发展。在特定的目标1中，将在左前降冠状动脉连接期间，在缺血再灌注的开胸兔模型中研究Ca2+瞬变的急性变化。在特定的目标2中，将在患有起搏引起的心力衰竭的狗中研究Ca2+瞬变的慢性变化。这些心脏多个位置的原位CA2+瞬变的时间和空间测量将提供有关异常Ca2+处理的机制，在缺血和心脏失败的情况下，异常的Ca2+处理有助于心脏功能障碍和心律失常。公共卫生相关性：在美国，心脏病和心力衰竭仍然是疾病和过早死亡的主要原因。钙会触发每次心跳过程中的收缩，钙调节在心脏病发作和心力衰竭后是异常的。在此提案中，我们将开发一种测量活动物心脏细胞中钙浓度的方法，并使用该技术更好地了解钙的异常如何导致心力衰竭和猝死。