MECHANISTIC STUDIES OF META IODOBENZYLGUANIDINE IN HEART

描述：I-131标记的间碘苄胍（MIBG）的动力学 将使用离体灌注的大鼠心脏模型研究心脏中的药物浓度。 将在各种条件下研究I-131-MIBG的摄取、保留和释放。 条件和相关的变量，如儿茶酚胺运输和 代谢、缺血和心脏代谢底物的变化。 神经元和神经元摄取将使用以下试剂区分， 阻断特定的摄取途径。 MIBG的综合数学模型 心脏中的动力学将被开发。 目标是定义 控制心脏中MIBG摄取的生理机制。 的 调查将试图澄清特定运输者的作用， 结合位点，并试图定义这些过程与1） 通过外部监测技术观察到的动力学行为，以及2） 内源性儿茶酚胺的相应处置正常和 缺血性疾病。

DESCRIPTION: The kinetics of I-131 labeled meta-iodobenzylguanidine (MIBG) in the heart will be studied using an isolated perfused rat heart model. Uptake, retention and release of I-131-MIBG will be studied under various conditions and correlated with variables such as catecholamine transport and metabolism, ischemia, and variations in cardiac metabolic substrate. Neuronal and extraneuronal uptake will be distinguished using agents that block specific uptake pathways. A comprehensive mathematical model of MIBG kinetics in the heart will be developed. The goal is to define the physiologic mechanisms that govern uptake of MIBG in the heart. The investigations will attempt to clarify the role of specific transporters and binding sites and seek to define the relationship of these processes to 1) the kinetic behavior observed by external monitoring techniques, and 2) the corresponding disposition of endogenous catecholamines in normal and ischemic conditions.