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; 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.'

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在人心脏的左心室壁中，大量神经纤维散布在心脏的肌肉细胞之间。大脑的脉冲导致神经从神经末端释放神经递质分子去甲肾上腺素。当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结合（称为“受体”）时，它会导致肌肉细胞更快，更大的力收缩，从而导致心脏泵送的血液量增加。在与受体结合后，神经的去甲肾上腺素分子被另一种称为“转运蛋白”的蛋白质备份以重复使用。放射性分子[11C]元羟基蛋黄酱（HED）在结构上与去甲肾上腺素相似，因此实际上相似，以至于神经端的转运蛋白也会将HED分子吸收到神经端。通过将其注射到患者的血液中，并使用一种称为正电子发射断层摄影仪（PET）摄像头的特殊成像装置将其积累的照片拍摄到心脏的神经中，临床医生可以获得表明心脏神经是否已受到疾病损害的图像。在神经在神经受损或破坏的区域中，神经正常且低的区域中，心脏中的HED吸收会很高。已经发现许多心脏和神经系统疾病会损害心脏神经，包括糖尿病，充血性心力衰竭，心肌梗塞和帕金森氏病。同样，越来越多的证据表明，受损的心脏神经可能是心脏猝死的根本原因。因此，人们对我们对许多不同疾病中心脏神经发生的变化的理解非常感兴趣。这项研究的主要目标是（1）更好地表征了正常健康受试者中HED的摄取和保留率； （2）研究HED对受试者年龄的依赖性。通过在健康志愿者的心脏中建立“正常” HED吸收水平的数据库，我们将能够更准确地表征许多在许多不同疾病中看到的对心脏神经的损害。最终，对这些疾病中神经损伤的更好理解可能会导致改善疗法，以停止疾病的进展，并可能逆转对心脏神经群体的损害。