[show abstract][hide abstract] ABSTRACT: 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.
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 micro g/kg/min intravenously). Each pig underwent 15 min of ischemia, twice per day for 5 d. Echocardiography and PET to determine myocardial glucose ((18)F-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.
Wall thickening in the circumflex region was lower than in remote regions in both groups. (18)F-FDG uptake in the circumflex region was similar in groups 1 and 2 (0.22 +/- 0.03 and 0.23 +/- 0.04 micro mol/min/g, respectively; not statistically significant). In the remote region, (18)F-FDG uptake was lower than in the circumflex region in group 1 (0.14 +/- 0.03 micro mol/min/g; P < 0.05) but was similar to that in the circumflex region in group 2 (0.20 +/- 0.03 micro mol/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.
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 (18)F-FDG studies have a limited role in discriminating postischemic from remote myocardium after dobutamine stress.
Journal of Nuclear Medicine 01/2003; 44(1):85-91. · 5.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: In patients with hibernating myocardium, regional uptake of the glucose analog 2-fluorine 18-fluoro-2-deoxy-d-glucose (FDG) is increased under resting conditions. It is unclear whether the degree of increased FDG uptake correlates with the degree of impaired blood flow response and whether chronic changes in the glucose transporters may play a role in the enhanced FDG uptake under fasted conditions.
Twelve swine were instrumented with a constrictor on the left anterior descending (LAD) artery. Serial echocardiography and positron emission tomography studies were done to assess temporal changes in myocardial function, blood flow, and FDG uptake. One week after surgery (early study), wall thickening, blood flow, and postdobutamine FDG uptake in LAD and remote territories were similar. By approximately 6 weeks (late study), baseline wall thickening in the LAD region was lower than in remote regions (20% +/- 7% and 36% +/- 6%, P <.05), as was dobutamine-stimulated blood flow (0.92 +/- 0.16 mL. min(-1). g(-1) and 1.17 +/- 0.20 mL. min(-1). g(-1) in LAD and remote regions, respectively; P <.05). After the dobutamine infusion, FDG uptake in the LAD region during fasted conditions was higher than in remote regions (0.128 +/- 0.053 micromol. min(-1). g(-1) and 0.098 +/- 0.044 micromol. min(-1). g(-1), respectively; P <.05), and the increase was proportional to the impairment in dobutamine blood flow (r(2) = 0.62, P <.001). After the animals were killed, the LAD region showed a higher content of GLUT4 by immunoblots and a greater degree of translocation as estimated by immunohistochemistry. In 5 additional hibernating pigs studied under resting fasted conditions, FDG uptake and GLUT4 translocation were also higher in the LAD region, in the absence of dobutamine stimulation.
In hibernating myocardium, regional FDG uptake under fasting conditions is higher than in remote regions, both at rest and after an infusion of dobutamine. The degree of poststress FDG uptake is proportional to the impaired stress-induced blood flow. Total GLUT4 content as well as membrane-bound protein is higher in the hibernating tissue, and these changes may facilitate the observed increase in FDG uptake.
Journal of Nuclear Cardiology 01/2003; 10(4):385-94. · 2.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: Repetitive myocardial ischemia increases glucose uptake, but the effect on glycogen is unclear. Thirteen swine instrumented with a hydraulic occluder on the circumflex (Cx) artery underwent 10-min occlusions twice per day for 4 days. After 24 h postfinal ischemia and in the fasted state, echocardiogram and positron emission tomography imaging for blood flow ([(13)N]-ammonia) and 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) uptake were obtained. Tissue was then collected for ATP, creatine phosphate (CP), glycogen, and glucose transporter-4 content, and hexokinase activity. After reperfusion, regional function and CP-to-ATP ratios in the Cx and remote regions were similar. Despite the absence of stunning, the Cx region demonstrated higher glycogen levels (33 +/- 11 vs. 24 +/- 11 micromol/g; P < 0.05), and this increase correlated well with the increase in FDG uptake (r(2) = 0.78; P < 0.01). Hexokinase activity was also increased relative to remote regions (0.62 +/- 0.29 vs. 0.37 +/- 0.19 IU/g; P < 0.05), with no difference in GLUT-4 content. In summary, 24 h after repetitive ischemia, glucose uptake and glycogen levels are increased at a time that functional and bioenergetic markers of stunning have recovered. The significant correlation between glycogen content and FDG accumulation in the postischemic region suggests that increased rates of glucose transport and/or phosphorylation are linked to increased glycogen levels in hearts subjected to repetitive bouts of ischemia.