Background-Modeling of the time-[1-C-11]acetate activity curve assumes constant concentration of labeled tricarboxylic acid cycle intermediates and associated metabolites, such as glutamate and aspartate, which may, however, decrease in short-term hibernating myocardium. Methods and Results-In 12 anesthetized pigs, [1-C-11]acetate was injected as a bolus into the cannulated left anterior descending coronary artery during normoperfusion, inotropic stimulation, ard early (5 to 45 minutes) and prolonged ischemia (60 to 90 minutes). Regional myocardial oxygen consumption (M(V) over dot O-2, microliters per minute per gram) was measured, and the absence of necrosis was verified by triphenyl tetrazolium chloride staining. Inotropic stimulation increased M(V) over dot O-2 from 52.5 +/- 7.4 to 195.4 +/- 36.2 (mean+/-SD) and the rate constant (k(mono), minutes(-1)) of [1-C-11]acetates clearance from 0.094 +/- 0.018 to 0.322 +/- 0.076. During early ischemia, M(V) over dot O-2 and k(mono) were decreased to 24.3 +/- 8.5 and 0.061 +/- 0.011, respectively. K-mono closely correlated to M(V) over dot O-2 during normoperfusion, inotropic stimulation, and early ischemia. In short-term hibernating myocardium, however, at an unchanged M(V) over dot O-2, k(mono) increased toward control values (0.080 +/- 0.014). Myocardial glutamate and aspartate concentrations (biopsies) decreased to 47 +/- 26% and 77 +/- 18%; the peak count rate decreased to 66 +/- 22% of its respective control value. After correction for the decreases in glutamate and aspartate or in peak count rate, k(mono) was again decreased (0.050 +/- 0.016 or 0.052 +/- 0.014, respectively), and a close relationship to M(V) over dot O-2 was restored. Conclusions-K-mono correlates to M(V) over dot O-2 in short-term hibernating myocardium when the decreases in aspartate and glutamate or in peak count rate are considered.