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Repetitive Supply-Demand Ischemia with Dobutamine Increases Glucose Uptake in Postischemic and Remote Myocardium

¹ Department of Medicine, VA Medical Center, University of Minnesota, Minneapolis, Minnesota
² Department of PET Imaging, VA Medical Center, University of Minnesota, Minneapolis, Minnesota
³ Department of Surgery, VA Medical Center, University of Minnesota, Minneapolis, Minnesota

The goal of this study was to determine whether myocardial glucose uptake after repetitive ischemia differs in response to coronary occlusion–reperfusion versus supply–demand ischemia induced by dobutamine. Although glucose metabolism is increased after myocardial ischemia, the metabolic effect of supply–demand ischemia induced by dobutamine may increase glucose metabolism within remote myocardium. This would make it difficult to discriminate postischemic from remote myocardium with glucose tracers. Methods: Eighteen swine with a hydraulic occluder and flow probe on the circumflex artery underwent repetitive ischemia. In group 1 (n = 9), the circumflex artery was occluded, whereas in group 2 (n = 9), circumflex flow was decreased by 30% before dobutamine (40 µg/kg/min intravenously). Each pig underwent 15 min of ischemia, twice per day for 5 d. Echocardiography and PET to determine myocardial glucose (¹⁸F-FDG) uptake were performed after final ischemia, and tissue was later analyzed for activation of Akt, p38 mitogen-activated protein, and adenosine monophosphate (AMP) kinase. Results: Wall thickening in the circumflex region was lower than in remote regions in both groups. ¹⁸F-FDG uptake in the circumflex region was similar in groups 1 and 2 (0.22 ± 0.03 and 0.23 ± 0.04 µmol/min/g, respectively; not statistically significant). In the remote region, ¹⁸F-FDG uptake was lower than in the circumflex region in group 1 (0.14 ± 0.03 µmol/min/g; P < 0.05) but was similar to that in the circumflex region in group 2 (0.20 ± 0.03 µmol/min/g; not statistically significant). AMP kinase activity in the remote region was significantly lower than in the circumflex region in group 1 but was similar to that in the circumflex region in group 2. Conclusion: Unlike repetitive coronary artery occlusion–reperfusion, repetitive supply–demand ischemia with dobutamine alters glucose uptake within the remote myocardium, possibly as a result of AMP kinase activation. Clinically, these data suggest that ¹⁸F-FDG studies have a limited role in discriminating postischemic from remote myocardium after dobutamine stress.

Key Words: myocardial ischemia • remote tissue • stunning • ¹⁸F-FDG; glucose metabolism

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