Ischemia impairs oxidative substrate metabolism as well as the mechanical and electrical functions of the myocardium. Previous investigations have shown an accelerated glycolytic flux in ischemic myocardium and have suggested that identification of residual glucose metabolic activity distinguishes hypoperfused, functionally impaired tissue from that which has been irreversibly injured due to antecedent infarction. With positron emission tomography (or PET) and labeled tracers of myocardial perfusion and glucose utilization, it is now possible to noniovasively assess both myocardial blood flow and glucose metabolism in vivo. The purpose of this investigation is to test the hypothesis that quantitative, noninvasive measurements of myocardial blood flow and, more importantly, glucose utilization, made with PET will more accurately reflect tissue viability (and therefore potential for myocardial salvage) than currently used clinical tests (electrocardiogram, analysis of segmental wall motion, thallium scinitgraphy). In Phase I, the applicant will gain experience in canine preparations of myocardial ischemia and infarction and validate tracer kinetic models reparations with the goal of making accurate, noninvasive measurements of myocardial blood flow (rubidium-82, N-13 ammonia) and glucose utilization (F-18 deoxyglucose in vivo with PET. Thus, during this phase the applicant will gain expertise in the basic aspects of PET technology. In Phase II, the tracer kinetic models developed will be validated in human subjects. Quantitative measurements of blood flow and glucose utilization made with PET would then be used to address the following questions: 1) To what extent may blood flow be reduced and yet support myocardial glucose metabolism? 2) Can noninvasive measurements of myocardial glucose utilization and blood flow made with PET predict improvement in segmental function following restoration of blood flow more successfully than the electrocardiogram, thallium scintigraphy, or analysis of wall motion? 3) To what extent can dietary state influence the uptake of glucose in ischemic myocardium? 4) Can quantitative measurements of blood flow and glucose utilization be used to assess the myocardial response to an ischemic insult and predict functional recovery? and 5) can quantitative measurements of blood flow and glucose utilization be used to predict long term prognosis in patients with ischemic heart disease?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL002022-02
Application #
3082454
Study Section
(SRC)
Project Start
1987-07-15
Project End
1992-07-14
Budget Start
1988-07-15
Budget End
1989-07-14
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Organized Research Units
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Porenta, G; Cherry, S; Czernin, J et al. (1999) Noninvasive determination of myocardial blood flow, oxygen consumption and efficiency in normal humans by carbon-11 acetate positron emission tomography imaging. Eur J Nucl Med 26:1465-74
Lin, K P; Huang, S C; Choi, Y et al. (1995) Correction of spillover radioactivities for estimation of the blood time-activity curve from the imaged LV chamber in cardiac dynamic FDG PET studies. Phys Med Biol 40:629-42
Di Carli, M F; Davidson, M; Little, R et al. (1994) Value of metabolic imaging with positron emission tomography for evaluating prognosis in patients with coronary artery disease and left ventricular dysfunction. Am J Cardiol 73:527-33
Czernin, J; Porenta, G; Brunken, R et al. (1993) Regional blood flow, oxidative metabolism, and glucose utilization in patients with recent myocardial infarction. Circulation 88:884-95
Czernin, J; Muller, P; Chan, S et al. (1993) Influence of age and hemodynamics on myocardial blood flow and flow reserve. Circulation 88:62-9
Porenta, G; Kuhle, W; Czernin, J et al. (1992) Semiquantitative assessment of myocardial blood flow and viability using polar map displays of cardiac PET images. J Nucl Med 33:1628-36
Brunken, R C; Mody, F V; Hawkins, R A et al. (1992) Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects. Circulation 86:1357-69
Nienaber, C A; Brunken, R C; Sherman, C T et al. (1991) Metabolic and functional recovery of ischemic human myocardium after coronary angioplasty. J Am Coll Cardiol 18:966-78
Mody, F V; Brunken, R C; Stevenson, L W et al. (1991) Differentiating cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy utilizing positron emission tomography. J Am Coll Cardiol 17:373-83
Chan, S Y; Brunken, R C; Phelps, M E et al. (1991) Use of the metabolic tracer carbon-11-acetate for evaluation of regional myocardial perfusion. J Nucl Med 32:665-72

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