MONOAMINERGIC INNERVATION IN NORMAL VOLUNTEERS STUDIED WITH MYOCARDIAL PET IMAGI

使用心肌 PET IMAGI 研究正常志愿者的单胺能神经支配

• 批准号: 7376640
• 负责人: DAVID M RAFFEL
• 金额: $ 0.46万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376640
• 关键词: heart; innervation

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.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在人类心脏的左室壁中，大量神经纤维散布在心脏的肌细胞之间。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。当从神经中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，它会导致肌肉细胞更快、更有力地收缩，导致心脏泵送的血量增加。在与受体结合后，去甲肾上腺素分子被神经带回以供重复使用，被另一类被称为“转运蛋白”的蛋白质所取代。放射性分子[11C]偏羟基麻黄碱(Hed)在结构上与去甲肾上腺素相似，事实上，神经末梢上的转运体也会将Hed分子吸收到神经末梢。通过将HED注射到患者的血液中，并使用一种名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积聚的照片，临床医生可以获得显示心脏神经是否因疾病而受损的图像。在神经正常的区域，心脏对HED的摄取会很高，而在神经受损或破坏的区域，HED的摄取会很低。许多心脏和神经疾病被发现会对心脏神经造成损害，包括糖尿病、充血性心力衰竭、心肌梗死和帕金森氏症。此外，越来越多的证据表明，心脏神经受损可能是心源性猝死的潜在原因。因此，增加我们对心脏神经在许多不同疾病中所发生的变化的了解是非常有兴趣的。这项研究的主要目的是(1)更好地描述正常健康受试者对HED的吸收和保持；(2)调查HED对受试者年龄的依赖性。通过建立一个关于健康志愿者心脏中广泛年龄的HED摄取水平的数据库，我们将能够更准确地描述在许多不同疾病中看到的心脏神经损伤的特征。最终，更好地了解这些疾病中的神经损害可能会导致改进的治疗方法，以阻止疾病的进展，并可能逆转对心脏神经群体的损害。