Effect of metabolic substrate on BMIPP metabolism in canine myocardium

Abstract

The lipid tracer 1 5-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) is clinically useful, and its basic metabolism is being analyzed. Because the pharmacokinetics of this lipid tracer may be affected by blood concentrations of fatty acid or glucose, this study evaluated the effects of excess levels of lipid or glucose on BMIPP uptake and metabolism.

Methods: A technique using an open-chest dog model was used. Blood sampling was performed from the left anterior descending coronary artery and great cardiac vein after an injection of 123I-BMIPP either with a glucose infusion (n = 6) or a lipid infusion (n = 5). High performance liquid chromatography and double-tracer kinetic analyses clarified the extraction, retention, backdiffusion and further metabolism of BMIPP. These results were compared with data from control dogs (n = 6).

Results: In this experiment, a 10-fold increase over the normal lipid blood concentration and twofold increase over the normal blood glucose concentration were evaluated with either intralipid or glucose infusion, respectively. In the lipid infusion studies, the extraction significantly decreased compared with the control values (74% +/- 12% to 58% +/- 8%; p < 0.05), and the washout increased from 50% +/- 13% to 68% +/- 16% (p < 0.05). The BMIPP backdiffusion increased (p < 0.05), and the levels of the further metabolites decreased (p < 0.05), while the retention level remained constant (normal, 89% +/- 9%; lipid infusion, 91% +/- 3%; ns). In the glucose infusion studies, the BMIPP extraction, retention and washout showed no statistical differences compared to controls; however, these parameters showed the same tendencies as those in the lipid infusion group. In addition, the BMIPP backdiffusion increased significantly (control, 25.1% +/- 8%; glucose infusion, 48.7% +/- 25.6%; p < 0.05) as it did after the lipid infusion.

Conclusion: BMIPP metabolism and uptake are affected by excess concentrations of lipid and glucose in the blood. However, the retention of BMIPP was not affected by either type of infusion. The BMIPP backdiffusion and the further metabolite comprising 10% of the tracer extracted were affected both by the lipid and glucose infusions. These results indicate that an excess fat concentration and glucose affect BMIPP uptake, especially the extraction of BMIPP and BMIPP backdiffusion.