MECHANISTIC STUDIES OF META IODOBENZYLGUANIDINE IN HEART

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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.