EVALUATION OF CARDIAC AUTONOMIC INNERVATION BY P E T

通过 PET 评估心脏自主神经支配

• 批准号: 3366748
• 负责人: DONALD M WIELAND
• 金额: $ 29.53万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1997-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3366748
• 关键词: autoradiography; diabetic neuropathy; electrophysiology; heart innervation; heart transplantation; histopathology; human subject; longitudinal human study; myocardium disorder; neurons; noninvasive diagnosis; positron emission tomography; radiotracer; ventricular fibrillation

Evaluation of the myocardial autonomic nervous system has previously been limited to animal models because of the unavailability of noninvasive methods, which could be used in humans. With the advent of radiopharmaceuticals which specifically delineate presynaptic and parasympathetic nerve terminals, integrity of the autonomic nervous system can be quantitatively assessed using positron emission tomography (PET). Animal studies have validated these new imaging approaches and initial clinical studies have provided excellent image quality necessary for the regional definition of tracer kinetics. This proposal will focus on the clinical application of neuronal imaging using PET in cardiac disease states which are known to affect the autonomic innervation of the heart. These studies will provide the base for the possible clinical application of these tracer approaches in the therapeutic management of patients. Initial studies with the catecholamine analogue C-11 hydroxyephedrine as well as parasympathetic tracer F-18 benzovesamicol will focus on the definition of tracer kinetics in the normal and denervated human heart. Incidence and time course in reinnervation of the human transplanted heart will be investigated since preliminary data suggest regional catecholamine uptake sites in patients with remote cardiac transplant. Longitudinal studies in patients with diabetic neuropathy using tracers for the sympathetic as well as the parasympathetic nervous system may elucidate the time course and natural history of autonomic dysfunction in this patient population. The major effort of this proposal will focus on the definition of the sympathetic and parasympathetic nervous system in patients with dilated cardiomyopathy. Regional myocardial kinetics of C-11 hydroxyephedrine will be used to quantitate the catecholamine storage capacity of the presynaptic neuron. Scintigraphic measurements will be correlated with regional electrophysiologic parameters such as effective refractory period and fibrillation threshold using electrophysiologic mapping techniques during open heart surgery. These functional measurements will be supplemented by tissue analysis for catecholamine content and histopathological integrity of the neuronal structures in corresponding sites. In addition, patients undergoing cardiac transplantation will undergo PET imaging prior to this procedure and the scintigraphic results will be compared with regional tissue analysis of the ex-planted cardiomyopathic heart using biochemical and autoradiographic techniques. This integrated approach using imaging technologies, electrophysiologic testing, and in-vitro tissue characterization including autoradiography will represent an unique definition of the autonomic nervous system in patients with various degree of dilated cardiomyopathy.

心肌自主神经系统的评估以前是 仅限于动物模型，因为无创的不可用 方法，可以用于人类。 随着出现 放射性药物，专门描述了突触前和 副交感神经终端，自主神经系统的完整性 可以使用正电子发射断层扫描（PET）进行定量评估。 动物研究已经验证了这些新的成像方法和初步 临床研究为您提供了出色的图像质量 示踪剂动力学的区域定义。 该建议将重点放在 使用PET在心脏病中使用神经元成像的临床应用 已知会影响心脏自主神经的状态。 这些研究将为可能的临床应用提供基础 在患者治疗管理中的这些示踪剂方法中。 对儿茶酚胺类似物C-11羟基甲酸酯的初步研究为 以及副交感示踪剂F-18苯并木霉醇将集中在 示踪剂动力学的定义在正常和被剥夺的人心脏中。 重新支配人类移植心脏的发病率和时间过程 由于初步数据表明区域儿茶酚胺 远程心脏移植患者的摄取部位。 纵向 使用示踪剂对糖尿病神经病患者进行研究 交感神经和副交感神经系统可能会阐明 该患者的自主功能障碍的时间课程和自然历史 人口。 该提案的主要努力将重点放在定义上 患者的交感神经和副交感神经系统 扩张的心肌病。 C-11的区域心肌动力学 羟基养殖将用于定量儿茶酚胺存储 突触前神经元的能力。 闪烁图测量将是 与区域电生理参数（例如有效）相关 使用电生理学的折射期和纤颤阈值 心脏手术期间的映射技术。 这些功能 将通过组织分析来补充儿茶酚胺的测量值 神经元结构的内容和组织病理学完整性 相应的站点。 此外，患有心脏的患者 移植将在此过程之前进行PET成像，并且 闪烁图结果将与区域组织分析进行比较 使用生化和放射自显影的前植入心肌疗法心脏 技术。 这种使用成像技术，电生理学的集成方法 测试和体外组织表征，包括放射自显影 将代表对自主神经系统的独特定义 患有不同程度扩张的心肌病的患者。