Contractile function is one of the most important determinants of prognosis in the post-infarction patient. Revascularization in the patient with regional dysfunction and viable myocardium may improve function whereas revascularization in the patient with non-viable myocardium would be of no benefit. An important management goal in patients with regional dysfunction therefore is to distinguish between dysfunctional myocardium which is viable myocardium would be of no benefit. An important management goal in patients with regional dysfunction therefore is to distinguish between dysfunctional myocardium which is viable and that which is not. Although this cannot be achieved by routine clinical diagnostic tests, prior work suggests that underlying metabolism may indicate viability, and therefore reversibility of contractile dysfunction with revascularization. Prior experimental studies suggest that cardiac high-energy phosphate metabolites (creatine phosphate [PCr] and ATP) are absent in non-viable tissue but nearly normal in dysfunctional """"""""stunned"""""""" and """"""""hibernating"""""""" myocardium. Recently, we and others have described non-invasive, spatially-localized 31P nuclear magnetic resonance (NMR) methodology for the determination of cardiac high-energy phosphate metabolite rations at rest and during handgrip and inotropic stresses in intact humans. This application proposes the implementation and testing of combined NMR spectroscopic and imaging with tissue """"""""tagging"""""""" techniques to study both absolute high-energy phosphate concentrations and contractile function in regions of dysfunctional myocardium. It also proposes the application of these combined techniques to two broad clinical studies; first, to determine the range and variability of absolute PCr and ATP levels in well- defined clinical paradigms of infarcted, stunned, or hibernating myocardium; and second, to prospectively determine whether absolute ATP and PCr levels can be used to predict reversibility of regional dysfunction following revascularization in reperfused myocardium. The experiments will be performed by a team of investigators with expertise in NMR spectroscopy and imaging on a clinical 1.5T whole-body MRI instrument equipped with broad-band spectroscopy and state-of-the-art imaging capabilities and located within the Johns Hopkins Hospital. It is clear that the ability to measure absolute PCr and ATP concentrations in a particular cardiac region, and to relate these concentrations to function in the same region would provide unique insights into the metabolic mechanisms and potential reversibility of contractile dysfunction in reperfused myocardium.
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