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Metabolism of Iodine-123-BMIPP in Perfused Rat Hearts

Central Research Laboratory, Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba
Tracer Kinetics, Biomedical Research Center, Osaka University Medical School, Suita, Osaka, Japan

Correspondence: For correspondence or reprints contact: Yoshihiro Yamamichi, Central Research Laboratory, Nihon Medi-Physics Co., Ltd., 3-1 Kitasode, Sodegaura, Chiba, 299-02, Japan.

ABSTRACT

Increased clinical use of ¹²³I-labeled 15-(p-iodophenyl)-3-(R,S)-methyl-pentadecanoic acid ([¹²³I]BMIPP) revealed discordance between BMIPP uptake and that of perfusion agents, which was inexplicable due to the uncertainty of its myocardial metabolism. This study clarifies the metabolic fate of BMIPP and its relation to substrates in isolated rat hearts. Methods: Rat hearts were perfused with 5 mmole/liter HEPES buffer containing various energy substrates and 1% bovine serum albumin. The buffer was recirculated for 4 hr after bolus injection of [¹²³I]BMIPP. Heart time-activity curves were monitored externally. After perfusion, the radioactivity in the heart and recirculated buffer was measured. The metabolites in the buffer were then extracted and analyzed by HPLC and TLC. Results: When 0.4 mmole/liter oleate was the energy substrate, more than eight radioactive BMIPP metabolites were detected. The metabolites in the coronary effluent depended on the energy substrate in the buffer. The radioactivity in the heart at the end of the perfusion period was significantly higher when 0.4 mmole/liter oleate (28.0% ± 1.2% ID/g, mean ± s.e.m.) or 10 mmole/liter glucose with 25 U/liter insulin (43.9% ± 2.2% ID/g) were the substrates compared to when 5 mmole/liter acetate (8.5% ± 0.4% ID/g) or 0.4 mmole/liter cold BMIPP (6.2% ± 0.3% ID/g) were the substrates. The distribution of metabolites suggests that oleate stimulated both alpha and beta oxidations, whereas glucose with insulin inhibited both. Acetate also stimulated alpha oxidation but not beta oxidation. Cold BMIPP strongly inhibited both alpha- and beta-oxidations, and little alpha oxidation occurred compared to beta-oxidation. Conclusion: These results suggest that [¹²³I]BMIPP is metabolized in the myocardium and the metabolism is closely related to myocardial carbohydrate utilization.

Key Words: fatty acid metabolism • iodine-123-BMIPP • alpha oxidation • beta oxidation • myocardial perfusion agents

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