MONOAMINERGIC INNERVATION IN NORM VOLUNTEERS STUDIED W/ MYOCARDIAL PET IMAGING

通过心肌 PET 成像研究正常志愿者的单胺能神经支配

• 批准号: 7603802
• 负责人: DAVID M RAFFEL
• 金额: $ 0.47万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603802
• 关键词: Age; Back; Binding; Blood; Blood Circulation; Brain; Cardiac; Cardiac Myocytes; Class; Computer Retrieval of Information on Scientific Projects Database; Congestive Heart Failure; Contracts; Databases; Dependence; Diabetes Mellitus; Disease; Disease Progression; Funding; Grant; Heart; Human; Image; Imaging Device; Institution; Lead; Left; Muscle Cells; Myocardial; Myocardial Infarction; Nerve; Nerve Endings; Nerve Fibers; Norepinephrine; Norepinephrine Receptors; Numbers; Parkinson Disease; Patients; Population; Positron-Emission Tomography; Proteins; Pump; Radioactive; Range; Research; Research Personnel; Resources; Source; United States National Institutes of Health; Ventricular; healthy volunteer; improved; interest; meta-hydroxyephedrine; nerve supply; nervous system disorder; neurotransmitter release; receptor; sudden cardiac death; uptake; volunteer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the left ventricular wall of the human heart, large numbers of nerve fibers are interspersed between the heart's muscle cells. Impulses from the brain cause the nerves to release the neurotransmitter molecule norepinephrine from the nerve endings. When the norepinephrine molecules that are released from the nerves bind to special proteins in the heart muscle cells (called "receptors"), it causes the muscle cells to contract more rapidly and with greater force, leading to an increase in the amount of blood being pumped by the heart. After binding to the receptors, norepinephrine molecules are taken back up by the nerves for reuse, by another class of proteins called "transporters". The radioactive molecule [11C]meta-hydroxyephedrine (HED) is structurally similar to norepinephrine, so similar in fact that the transporters on the nerve endings also will take up HED molecules into the nerve endings. By injecting HED into a patient's bloodstream, and taking pictures of its accumulation into the nerves of the heart with a special imaging device known as a positron emission tomography (PET) camera, clinicians can obtain images that show whether the nerves of the heart have been damaged by disease. HED uptake in the heart will be high in regions where the nerves are normal and low in regions where the nerves have been damaged or destroyed. Many heart and neurological diseases have been found to cause damage to the nerves of the heart, including diabetes, congestive heart failure, myocardial infarction, and Parkinson's disease. Also, there is increasing evidence that damaged cardiac nerves may be an underlying cause to sudden cardiac death. Therefore there is great interest in increasing our understanding of the changes that occur to cardiac nerves in many different diseases. The primary objectives of this study are (1) to better characterize the uptake and retention of HED in normal healthy subjects; and (2) to investigate the dependence of HED on the age of the subject. By establishing a database of "normal" HED uptake levels in the hearts of healthy volunteers over a wide range of subject ages, we will be able to more accurately characterize the damage to cardiac nerves that is seen in many different diseases. Ultimately, a better understanding of the nerve damage in these diseases may lead to improved therapies for halting the progression of the disease, and possibly reversing the damage to cardiac nerve populations.'

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在人类心脏的左心室壁中，心脏的肌肉细胞之间散布着大量的神经纤维。来自大脑的冲动导致神经从神经末梢释放神经递质分子去甲肾上腺素。当从神经释放的去甲肾上腺素分子与心肌细胞中的特殊蛋白质（称为“受体”）结合时，会导致肌肉细胞收缩得更快、力度更大，从而导致血液量增加由心脏泵动。与受体结合后，去甲肾上腺素分子被神经重新吸收，并被另一类称为“转运蛋白”的蛋白质重新利用。放射性分子[11C]间羟基麻黄碱（HED）在结构上与去甲肾上腺素相似，实际上非常相似，以至于神经末梢上的转运蛋白也会将HED分子吸收到神经末梢中。通过将 HED 注射到患者的血液中，并使用一种称为正电子发射断层扫描 (PET) 相机的特殊成像设备拍摄其在心脏神经中的积累情况，临床医生可以获得显示心脏神经是否受到损伤的图像。因疾病而受损。心脏中神经正常的区域的 HED 摄取量较高，而神经受损或破坏的区域的 HED 摄取量较低。已发现许多心脏和神经系统疾病会对心脏神经造成损害，包括糖尿病、充血性心力衰竭、心肌梗塞和帕金森病。此外，越来越多的证据表明，受损的心脏神经可能是心源性猝死的根本原因。因此，人们对增加我们对许多不同疾病中心脏神经发生的变化的了解非常感兴趣。本研究的主要目标是 (1) 更好地表征正常健康受试者对 HED 的摄取和保留； (2) 研究 HED 对受试者年龄的依赖性。通过建立不同年龄范围的健康志愿者心脏中“正常”HED 摄取水平的数据库，我们将能够更准确地描述许多不同疾病中出现的心脏神经损伤特征。最终，更好地了解这些疾病中的神经损伤可能会导致改进治疗方法，以阻止疾病的进展，并可能扭转对心脏神经群的损伤。