Delineation of myocardial oxygen utilization with carbon-11-labeled acetate.

Abstract

Although positron-emission tomography (PET) with labeled fatty acid delineates infarct size and permits qualitative assessment of fatty acid utilization, quantification of oxidative metabolism is limited by complex alterations in the pattern of utilization of fatty acid during ischemia and reperfusion. Because metabolism of acetate by myocardium is less complex than that of glucose or palmitate, we characterized kinetics of utilization of radiolabeled acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit buffer and performed a pilot tomographic study in man.Results of initial experiments with carbon-14-labeled acetate ("4C-acetate) indicated that the steadystate extraction fraction of acetate averaged 61.5 + 4.0% in control hearts (n = 4), 93.6 ± 0.9% in hearts rendered ischemic (n = 4), and 54.8 + 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation of "4C-acetate, assessed from the rate of efflux of "4CO2 in the venous effluent, correlated closely with the rate of oxygen consumption under diverse metabolic conditions (r = .97, p < .001). In addition, no significant differences were observed between rates of efflux of total 14C in all chemical species (reflecting total clearance of tracer from myocardium) and efflux of 4'CO2.

Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium.

“…Rate constants for myocardial [1-'1C]acetate clearance correlated well with oxygen consumption. 4 Recent studies5 in our group with PET after intra- 20 mg/kg initially and sodium pentobarbital as needed to maintain anesthesia, intubated, and ventilated with room air by a respirator (Harvard Apparatus, Millis, Massachusetts). Catheters were advanced into the aorta through one femoral and one carotid artery for blood pressure monitoring and withdrawal of arterial blood.…”

Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes

“…Results from the moderation regression analysis showed that age blunted the relationship between peak BAT 11 C radioactivity and fractional (b 2 = 20.28, P = 0.04) and net glucose uptake by BAT (b 2 = 20.31, P = 0.04) ( Supplementary Tables 1 and 2). The monoexponential decay slope from tissue peak 11 C activity ( 11 C-acetate k), an index of tissue oxidative metabolism (28,29), increased during cold exposure in all participants (Fig. 3E).…”

Evaluation of Fatty Acid .BETA.-Oxidation in Patients With Prior Myocardial Infarction in Relation to Myocardial Blood Flow, Total Oxidative Metabolism, and Left Ventricular Wall Motion

“…3,5,[12][13][14][15][16][17] A monoexponential curve was also applied to the phase of decreasing 11 C-acetate activity after it had reached its peak count. In the 11 C-acetate PET study, a monoexponential curve fitted the time -activity curve well in all regions.…”

“…5,[12][13][14][15][16][17][20][21][22] The clearance rate constant Kmono, calculated by applying a monoexponential equation to the clearance curve of 11 C-acetate, has been used as an index of regional myocardial oxidative capacity. 3,5,[12][13][14][15][16][17] On the other hand, fatty acid metabolism can be estimated noninvasively using 11 C-palmitate PET. Several investigators have reported that the clearance curve of 11 Cpalmitate is bi-exponential: the early rapid phase reflects -oxidation of fatty acid and the late slow phase represents turnover of the esterified lipid pool.…”