Myocardial metabolism of I-123-BMIPP in a canine model with ischemia: Implications of perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease

I-123-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) is a fatty ac id analog for SPECT imaging. This radiopharmaceutical possesses the unique property, that is, perfusion-metabolism mismatch on SPECT images in patient s with ischemic heart disease. However, the reason of this mechanism remain s unclear. Methods: Using open-chest dogs under anesthesia, we made a syste m to release all the blood of the great cardiac vein outside without recirc ulation, if necessary. Left anterior descending artery (LAD) was occluded f or 30 min after reperfusion. After the injection of BMIPP into LAD, blood s amplings from the cardiac vein and abdominal aorta (6 dogs) or serial biops y specimens from the LAD region (5 dogs) were performed, and then compared with the normal control. The catabolites of BMIPP, including backdiffusion of nonmetabolized BMIPP, were evaluated with high-performance liquid chroma tography (HPLC) in the efflux study. Thin-layer chromatography (TLC) techni que was introduced in the tissue analytical study. Results: Although the ra pid extraction of BMIPP from the plasma into the myocardium and the subsequ ent retention were unchanged, the early washout (8 min) of radioactivity si gnificantly increased (51% +/- 12% to 65% +/- 7%; P < 0.05) with ischemia. The metabolites from the myocardium consisted of backdiffusion of nonmetabo lized BMIPP, a, intermediate, and full oxidation metabolites. Among these m etabolites, backdiffusion of nonmetabolized BMIPP in blood significantly in creased (27.9% +/- 7.7% to 42.3% +/- 8.1%; P < 0.05), especially in the ear ly phase with ischemia. In tissue, the radioactivity was concentrated in th e triglyceride pool even in the early phase, and in addition, BMIPP and alp ha-oxidized metabolite significantly decreased in the early phase with isch emia (t = 1 min after BMIPP injection, 25.9% +/- 8.6% to 14.5% +/- 2.1%, P < 0.01; t = 2 min, 8.9% +/- 5.0% to 4.5% +/- 1.7%, P < 0.05). Conclusion: T hese results show that backdiffusion of nonmetabolized BMIPP from the myoca rdium increased and BMIPP (long-chain fatty acids) in tissue decreased with ischemia, suggesting backdiffusion of nonmetabolized BMIPP might play an i mportant role in myocardial perfusion-metabolism mismatch on SPECT images i n patients with ischemic heart disease.