The determination of relative myocardial thallium activity as a function of time in sequential imaging studies is being increasingly used in the clinical setting for the detection or evaluation of coronary artery disease. The temporal behavior of myocardial thallium concentration is necessarily related to the balance of myocardial uptake and intrinsic washout, yet the relationship of these kinetic parameters to normal and ischemic states has yet to be determined. The overall objective of this proposal is to provide a logical framework for understanding and interpreting various patterns of thallium uptake and redistribution, and to measure the important transport coefficients as a function of altered perfusion states and MVO2. The possibility of using kinetic exchange rates of thallium as a means of quantitating the functional degree of severity of coronary artery stenoses will also be explored. Experiments will be carried out in canine models in order, 1) to determine extraction fraction values for thallium as a function of myocardial blood flow, 2) To measure intrinsic myocardial washout rates of thallium-201 under various physiologic conditions which alter either myocardial blood flow, MVO2 or both, 3) To determine the effects of these alterations on myocardial uptake and redistribution following intravenous injection of the radionuclide, and 4) to measure intrinsic myocardial thallium washout rates in patients following direct intracoronary injection and to relate these measurements to the degree of coronary artery narrowing and regional wall motion abnormalities. It is expected that the information obtained from these canine and patient studies will provide a fundamental basis for the understanding and proper utilization of myocardial thallium kinetics for scintigraphic assessment of patients with suspected or recognized coronary artery disease.