Elsevier

Journal of Nuclear Cardiology

Volume 10, Issue 4, July–August 2003, Pages 385-394
Journal of Nuclear Cardiology

Myocardial glucose uptake after dobutamine stress in chronic hibernating swine myocardium

https://doi.org/10.1016/S1071-3581(03)00431-8Get rights and content

Abstract

Background

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.

Methods and results

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 μmol · min−1 · g−1 and 0.098 ± 0.044 μmol · min−1 · g−1, respectively; P < .05), and the increase was proportional to the impairment in dobutamine blood flow (r2 = 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.

Conclusions

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.

Section snippets

Methods

This study was performed under the guidance of the animal care committee at the VA Medical Center (Minneapolis, Minn) and conforms with the US National Institutes of Health “Guide for the Care and Use of Laboratory Animals” (publication No. 85-23, revised 1996).

Regional myocardial function at baseline

During the early study, systolic wall thickening at baseline was similar in the LAD and remote regions. During the late study, an anterior wall motion abnormality was evident and systolic wall thickening in the LAD region at baseline was lower than in the remote region (P < .05) (Figure 1). During the initial echocardiographic study, end-diastolic wall thickness in the LAD and remote regions was 0.78 ± 0.05 cm and 0.77 ± 0.06 cm, respectively (P = not significant [NS]). During the final

Discussion

The principal findings of this study are as follows. First, myocardial FDG uptake in chronic hibernating myocardium is higher than in remote regions after an infusion of dobutamine, and the increased glucose metabolic activity is proportional to the relative impairment in dobutamine-induced blood flow. Second, the abnormalities in poststress FDG uptake are associated with changes in GLUT4, including increased total content by immunoblotting and enhanced translocation by immunohistochemistry.

Acknowledgements

The authors have indicated they have no financial conflicts of interest.

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    This study was supported in part by General Medical Research funds (E.O.M.) from the US Department of Veterans Affairs.

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