METABOLISM OF IODINE-123-BMIPP IN PERFUSED RAT HEARTS

Increased clinical use of I-231-labeled 15-(p-iodophenyl)-3-(R,S)methy l-pentadecanoic acid ([[I-123]BMIPP) revealed discordance between BMIP P uptake and that of perfusion agents, which was inexplicable due to t he 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 bu ffer containing various energy substrates and 1% bovine serum albumin. The buffer was recirculated for 4 hr after bolus injection of [I-123] BMIPP. Heart time-activity curves were monitored externally. After per fusion, the radioactivity in the heart and recirculated buffer was mea sured. The metabolites in the buffer were then extracted and analyzed by HPLC and TLC. Results: When 0.4 mmole/liter oleate was the energy s ubstrate, more than eight radioactive BMIPP metabolites were detected. The metabolites in the coronary effluent depended on the energy subst rate in the buffer. The radioactivity in the heart at the end of the p erfusion 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 2 5 U/liter insulin (43.9% +/- 2.2% ID/g) were the substrates compared t o when 5 mmole/liter acetate (8.5% +/- 0.4% ID/g) or 0.4 mmole/liter c old BMIPP (6.2% +/- 0.3% ID/g) were the substrates. The distribution o f metabolites suggests that oleate stimulated both alpha and beta oxid ations, whereas glucose with insulin inhibited both. Acetate also stim ulated alpha oxidation but not beta oxidation. Cold BMIPP strongly inh ibited both alpha- and beta-oxidations, and little alpha oxidation occ urred compared to beta-oxidation. Conclusion: These results suggest th at [I-123]BM]PP is metabolized in the myocardium and the metabolism is closely related to myocardial carbohydrate utilization.