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Serial Changes in ¹⁴C-Deoxyglucose and ²⁰¹Tl Uptake in Autoimmune Myocarditis in Rats

Division of Tracer Kinetics, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka; and Department of Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan

This study was designed to examine the relationships between the uptake of ¹⁴C-deoxyglucose (DG) and the uptake of ²⁰¹Tl in a rat model of autoimmune myocarditis. Methods: Autoimmune myocarditis was induced in normal rats by immunization with pig cardiac myosin. Dual-tracer autoradiography with DG and ²⁰¹Tl was performed on frozen slices of the animals’ hearts 3 wk (acute phase), 8 wk (subacute phase), and 14 wk (chronic phase) (each n = 5) after immunization. The extent of inflammatory damage was classified histologically into three categories on the basis of cell infiltration: mild (Mi), moderate (Mo), and severe (Sv). The regional count in the region of interest set on the autoradiogram was normalized on the basis of that of control rats. The ratio of total cardiac uptake to the injected dose (%ID/g x BW, where ID is injected dose and BW is body weight) was calculated by tissue counting. Expressions of glucose transporters GLUT1 and 4 were evaluated by the enzyme-labeled antibody method. Results: The total cardiac uptake of DG in the acute phase of myocarditis was significantly higher than in normal control rats (3.43% ± 0.92% vs. 0.97% ± 0.38%; P < 0.0001); it then decreased in the chronic phase but was still higher than in the controls (1.85% ± 0.37% vs. 0.97% ± 0.38%; P < 0.01). The total cardiac uptake of ²⁰¹Tl in the acute phase of myocarditis was significantly lower than in the controls (7.4% ± 0.7% vs. 12.0% ± 3.3%; P < 0.005); it then increased in the chronic phase and reached normal levels (13.0% ± 3.3% vs. 12.0% ± 3.3%; not significant [NS]). In the acute phase, the regional uptakes of DG in the Mi, Mo, and Sv regions were 143.1% ± 107.9%, 169.6% ± 59.9%, and 317.5% ± 103.3%, respectively, whereas those of ²⁰¹Tl were 88.4% ± 31.9%, 72.1% ± 34.6%, and 48.4% ± 21.5%, respectively. GLUT expression was evaluated visually and classified into four grades (0, 1, 2, and 3). In the acute phase, GLUT1 expression was higher in rats in the Sv group than in the controls (2.87 vs. 0.87). GLUT4 was not expressed in the Sv areas but was found in the Mi areas. Conclusion: In the acute phase of autoimmune myocarditis in rats, cardiac uptake of DG was accelerated by severe inflammation. Cardiac uptake of ²⁰¹Tl, on the other hand, was suppressed. Our results suggest that GLUT1 expression accelerates DG uptake by cells in areas of severe inflammation.

Key Words: autoimmune myocarditis • ¹⁴C-deoxyglucose • ²⁰¹Tl • glucose transporter • autoradiography

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