Regional myocardial oxygen consumption determined noninvasively in humans with [1-11C]acetate and dynamic positron tomography.

Abstract

Experimental studies of animals have previously demonstrated the validity of [1-ttClacetate as a tracer of oxidative metabolism for use with positron emission tomography. The present study was undertaken to define in normal human volunteers the relation between myocardial clearance kinetics of [1-"C]acetate, and the rate-pressure product as an index of myocardial oxygen consumption. Twenty-two studies were performed of 12 volunteers. The rate-pressure product was increased with continuous supine bicycle exercise in six studies. Of the 16 resting studies, seven were performed in the fasted state and nine following an oral glucose load, to define possible effects of substrate availability on the tracer-tissue kinetics. Myocardial tissue time-activity curves were biexponential. Clearance of activity was homogeneous throughout the myocardium. The rate constants ki, obtained from biexponential fitting, and kn..n, obtained by monoexponential fitting of the initial linear portion of the time-activity curves, correlated well with the rate-pressure product. Although the correlation coefficient was higher for kl than for km.,, (0.95 vs. 0.91), analysis on a sectorial basis showed less regional variability in kn..O. This suggests that korno,0 which is more practical than kl because it requires shorter acquisition times, may be more clinically and experimentally useful for detection of myocardial segments with abnormal oxygen consumption. Overall, changes in myocardial substrate supply were without significant effect on the relation between the rate constants (kl and k...0) and the rate-pressure product, although a small decrease in km0,,0/rate-pressure product was observed following oral glucose by paired analysis in four subjects. It is concluded that [1-"C]acetate can be used for the noninvasive measurement of myocardial oxygen consumption in humans with positron emission tomography, and, thus, has clinical and experimental potential as a tool for the understanding and diagnosis of myocardial disease. (Circulation 1989;80:863-872) acid kinetics in myocardium.3-12 Although characteristic changes in uptake and clearance of labeled fatty acids have been observed in myocardial ischemia, these changes reflect the net effect of diminished oxygen supply on each of the steps in fatty acid utilization and are not specific for impairment of 3-oxidation.2 Uptake and clearance of labeled fatty acids are markedly affected by substrate availability,13-15 in addition to myocardial workload.16 To characterize more precisely the metabolic state of the myocardium, a selective tracer of mitochondrial oxidative function is required.In the early 1980s, [1-1"C]acetate was examined both in animal studies17 and in patients with coro-

Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart.

“…An understanding of the quantitative extent of these alterations is important for both diagnosis and therapy in reperfused myocardium. For example, clearance of "C-enriched acetate may be monitored in patients by positron tomography (7)(8)(9), yet the biochemical basis of altered tracer clearance during ischemia is incompletely understood (10)(11)(12). Of perhaps greater significance is the potential for improving recovery after ischemia by deliberately modifying carbon flow into the citric acid cycle.…”

Myocardial O2consumption in porcine left ventricle is heterogeneously distributed in parallel to heterogeneous O2delivery

“…However, direct measurement of aerobic metabolic flux in small myocardial regions became possible only recently. Regional V O 2 and regional blood flow can be estimated with PET, although this technique still does not permit analysis at sufficiently high spatial resolution to study cardiac heterogeneity in small tissue areas (1,34,37).To investigate the distribution of MV O 2 at high spatial resolution, a new combination of isotope labeling protocol and mathematical analysis of 13 C incorporation into the tricarboxylic acid (TCA) cycle has been developed by us (43). …”

11C-Acetate Clearance as an Index of Oxygen Consumption of the Right Myocardium in Idiopathic Pulmonary Arterial Hypertension: A Validation Study Using 15O-Labeled Tracers and PET

“…In such cases, 11 C-acetate clearance may severely overestimate adenosine triphosphate resynthesis and underestimate MVO 2 . On the other hand, earlier studies with healthy volunteers and experimental canine studies showed that changes in the availability of myocardial metabolic substrates or ischemia, without changes in hemodynamics, did not affect LV 11 C-acetate kinetics, with similar relationships between K mono and either MVO 2 or RPP at normal baseline conditions (23)(24)(25).…”

“…In the present study, test-retest variability was not investigated, as adding a scan was not feasible for the present patient population. The reproducibility of 11 C-acetate clearance rate measurements in humans has been demonstrated by Armbrecht et al (24). The fact that the measurement of pulmonary artery pressure and heart rate for the calculation of RPP was performed on another day may also have contributed to error variance.…”