The evaluation of myocardial perfusion and metabolism plays an important role in the diagnosis and treatment of all types of heart disease. Noninvasive techniques that could make such determinations utilizing standard external imaging devices would enhance the availability of patient studies and potentially reduce their cost. Therefore, the long- term objectives of this study are to develop a better understanding of the basic characteristics of radionuclide compounds that can assess myocardial blood flow and functional state.
The specific aims of this study are to evaluate the myocardial uptake, washout, extraction and compartmental distribution of several different perfusion agents (including thallium, rubidium, technetium labeled analogs of isonitriles and boronic acid adducts of technetium oximes [BATO's]) as well as radioiodinated fatty acid analogs (as available) in an isolated rabbit heart model during varied levels of coronary perfusion and alterations in cellular metabolism. In other experiments the intracellular binding characteristics of these agents will be determined. In these studies blood perfused hearts will be employed having constant flow during each transport measurement. After control determination variable intervention (flow, hypoxia, ATPase inhibition, etc.) can be performed and isotope transport measurements can be repeated for comparative purposes. Coronary venous samples are collected at timed intervals and are subsequently measured to determine myocardial isotope uptake, clearance and extraction. Special chemical separation techniques will be used to analyze the distribution of isotope in heart tissue. Additional studies will evaluate tracer deposition in heart tissue, utilizing autoradiographic techniques. The medical significance of this work will be that the results obtained from this basic research will provide the information needed to understand the cardiac transport of these tracers. This information can then be used to formulate the methods for performing and interpreting myocardial imaging of these agents alone, and in combination with other imaging agents. These methods could be likely to attain widespread clinical utility.
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