POSITRON TOMOGRAPHY IN ISCHEMIC HEART DISEASE

拟议研究的统一主题是血流代谢

The unifying theme of the proposed research is the blood flow metabolism mismatch as observed with position emission tomography as a sign of myocardial viability in patients with ischemic heart disease. Initially reported from our laboratory, the existence of this pattern has been confirmed by and is now being employed by other investigators. However, questions regarding the underlying pathophysiology of preserved glucose metabolism in dysfunctional myocardium and its clinical relevance remain. The proposed research will employ newly developed noninvasive methods for quantifying regional rates of blood flow, glucose utilization, oxygen consumption, protein synthesis and for evaluation of fatty acid metabolism and for mapping the spatial distribution of these processes and to determine geographic extent and severity of abnormalities. This will be accomplished by high temporal and spatial resolution positron emission tomographic imaging of the arterial input function and myocardial uptake of N-13 ammonia, F-18 2-deoxyglucose, C-11 palmitate, C-11 acetate and C-11 labeled amino acids. The multi-slice capability of the new PET scanner will further be used for defining the spatial distribution of these functional process in the left ventricular myocardium. With these tools, the research will explore and define different mechanisms that might account for the observed blood flow metabolism mismatch pattern as for example "hibernation" versus "stunning" delineate associated abnormalities in blood flow, oxidative metabolism and fatty acid oxidation and their relation to regional and global left ventricular function. The research will further examine the prognostic significance of these metabolic abnormalities in patients with coronary artery disease who are of these metabolic abnormalities and their temporal and spatial changes in chronic ischemic heart disease or after an acute myocardial infarction and their recovery after interventional restoration of blood flow. The research will also determine rates of protein synthesis in ischemic, post-ischemic and normal myocardium in patients with coronary artery disease before and after coronary interventions and after acute myocardial infarction. The results are likely to provide new insights into the pathophysiology of human myocardial ischemia and should prove clinically equally useful for improved and more accurate delineation of severity and extent of ischemically compromised myocardium as well as for therapeutic decisions in patients with coronary artery disease and regional and global left ventricular dysfunction.