In the United States an estimated 550,000 coronary artery bypass grafting and percutaneous transluminal coronary angioplasty procedures are performed annually at a direct cost of over 6 billion dollars. Optimal utilization of these resources requires the accurate identification of patients likely to benefit from these interventions. Unfortunately, this has proven to be a vexing problem, particularly in patients with left ventricular dysfunction secondary to chronic or acute ischemic syndromes. Accordingly, this project is designed to assess perfusion and metabolism in myocardium that is mechanically dysfunctional due to ischemia in order to identify biologic determinants of a favorable response to myocardial revascularization. Once identified, optimal measurements of these determinants will be incorporated into an algorithm designed to permit prospective identification of patients likely to benefit from myocardial revascularization. We propose to study patients with: significant resting left ventricular dysfunction due to chronic coronary artery disease; recent myocardial infarction (MI) treated with thrombolytic agents; and recent MI not treated with thrombolytic agents. The patients will be studied with positron emission tomography (PET), and alterations in regional myocardial perfusion (using H215O), glucose metabolism (using [18F]-2-fluoro-2-deoxyglucose), and oxidative metabolism (using 11C- acetate) will be characterized and referenced to regional myocardial contractile performance (measured echocardiographically) at rest, both before and after myocardial revascularization. The objectives of this project are entirely consistent with the long-term goals of the program project to develop approaches utilizing cyclotron-produced radiopharmaceuticals for clinical investigation and potentially for use in clinical medicine. The data obtained should help delineate the determinants of a successful outcome following coronary revascularization as well as finding those parameters that will optimize patient selection for these procedure. Moreover, the proposed research has the potential to provide a new reference standard for dysfunctional-viable myocardium that will facilitate development and evaluation of indexes obtainable with more universally available procedures that can be used to evaluate the efficacy of new therapeutic strategies designed to restore nutritive perfusion to ischemic myocardium.
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