PET NEURONAL TRACES KINETICS IN ISOLATED DISEASED HEARTS

PET 神经元追踪离体患病心脏的动力学

• 批准号: 2839094
• 负责人: DAVID M RAFFEL
• 金额: $ 9.91万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-17 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2839094
• 关键词: amines; bioimaging /biomedical imaging; blood chemistry; carbon; catecholamines; diabetic neuropathy; disease /disorder model; doxorubicin; drug metabolism; heart disorder diagnosis; heart failure; heart innervation; laboratory rat; mechanical pressure; membrane transport proteins; nervous system disorder diagnosis; neurons; noninvasive diagnosis; norepinephrine; pharmacokinetics; positron emission tomography; radiotracer; streptozotocin; sympathetic nervous system; tissue /cell culture

DESCRIPTION: (Adapted from the applicant's abstract) The structurally related norepinephrine analogues [C-11]meta-hydroxyephedrine, [C-11]phenylephrine, and [C-11]epinephrine have been developed as radiotracers for non-invasive imaging studies of cardiac sympathetic innervation using positron emission tomography (PET). Striking alterations in the kinetic behavior of these neuronal tracers have been seen in PET studies of patients with diabetic autonomic neuropathy and heart failure. Associating the altered tracer kinetics with specific neuronal abnormalities has been difficult, as several hypothetical changes in neuronal function could cause such alterations. The major goal of the proposed studies is to correlate changes in the kinetics of these radiotracers to specific neuronal changes in cardiac sympathetic neurons using rat models of diabetic autonomic neuropathy and heart failure. The proposed studies will build on an existing foundation of kinetic studies performed in the isolated working rat heart. Kinetic studies in hearts isolated from rat models of diabetes and heart failure will be used to assess the sensitivity of the tracer kinetics to pathology-induced changes in cardiac sympathetic nerve populations. Following the tracer kinetic studies, direct in vitro measurements of several key components of cardiac sympathetic neurons will be performed in the same hearts to characterize the extent and severity of the pathology-induced neuronal changes. The in vitro studies will include determinations of the densities of neuronal norepinephrine transporters (NET) and vesicular monoamine transporters (VMAT), as well as tissue catecholamine levels. By identifying correlations between the kinetic data and the in vitro findings, insight into the specific underlying causes of perturbations in the tracer kinetics may be gained. This information should assist clinicians, who are studying cardiac sympathetic neurons with these agents, to interpret their clinical findings. In addition, these studies will provide new information concerning the affects of these diseases upon cardiac sympathetic nerve populations.

描述：（改编自申请人的摘要）结构上 相关去甲肾上腺素类似物[C-11]间羟基麻黄碱， [C-11]去氧肾上腺素和[C-11]肾上腺素已被开发为 用于心脏交感神经非侵入性成像研究的放射性示踪剂 使用正电子发射断层扫描（PET）进行神经支配。 引人注目的改变 在 PET 中观察到这些神经元示踪剂的动力学行为 糖尿病自主神经病变和心力衰竭患者的研究。 将改变的示踪动力学与特定的神经元异常相关联 一直很困难，因为神经元功能的一些假设变化 可能会导致这样的改变。 拟议研究的主要目标是 将这些放射性示踪剂的动力学变化与特定的神经元相关联 使用糖尿病大鼠模型观察心脏交感神经元的变化 自主神经病变和心力衰竭。 拟议的研究将建立在 在隔离工作中进行的动力学研究的现有基础 老鼠的心。 从糖尿病大鼠模型分离的心脏的动力学研究 心力衰竭将用于评估示踪剂的敏感性 心脏交感神经病理学变化的动力学 人口。 示踪动力学研究后，直接在体外 心脏交感神经元几个关键组成部分的测量将 在同一颗心脏中进行，以表征心脏的程度和严重程度 病理引起的神经元变化。 体外研究将包括 神经元去甲肾上腺素转运蛋白密度的测定 (NET) 和囊泡单胺转运蛋白 (VMAT)，以及组织 儿茶酚胺水平。 通过识别动力学数据之间的相关性 和体外研究结果，深入了解具体的根本原因 可能会获得示踪动力学的扰动。 该信息应 协助临床医生研究心脏交感神经元 剂，以解释他们的临床发现。 此外，这些研究 将提供有关这些疾病对人的影响的新信息 心脏交感神经群。