To assess its potential role as a new metabolic probe, the relationship between regional uptake of the 15-(p-[I-125]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) fatty acid analog and myocardial blood Row was studied. Methods: In 14 open-chest dogs, the left anterior descending coronary artery was cannulated and extracorporal bypass-perfused at normal (control group; n = 4) and reduced flow (intervention group; n = 10). Myocardial blood flow (MBF) was assessed with Sc-46-labeled microspheres. Forty minutes after intravenous injection of DMIPP, the heart was excised and cut into 120 samples. In each sample, MBF ml.g(-1).min(-1) and DMIPP uptake (percentage of the injected dose per gram, %ID/g) were assessed. Results: In normal myocardium, MBF and DMIPP uptake were 1.10 +/- 0.18 ml.g(-1).min(-1) and 1.18 +/- 0.42 x 10(-2) %ID/g, respectively. In the extracorporal bypass area, flow was reduced to 0.49 +/- 0.20 ml.g(-1).min(-1) (p < 0.0001 compared to normal), and DMIPP uptake was decreased to 0.75 +/- 0.26 x 10(-2) %ID/g (p < 0.0001 compared to normal). DMIPP uptake and MBF positively correlated in normal (DMIPP uptake = 0.77 +/- 0.23.MBF; r = 0.41; p < 0.0001) and hypoperfused (DMIPP uptake = 0.35 +/- 0.70.MBF; r = 0.63; p < 0.0001) myocardium. The heterogeneity, indicated by the coefficient of variation, in normal myocardium was 0.23 +/- 0.05 for MBF and was lower(p < 0.0001) for DMIPP uptake: 0.13 +/- 0.05. During flow reduction, heterogeneity increased significantly (p < 0.0001) for both MBF(0.59 +/- 0.22) and DMIPP uptake (0.37 +/- 0.23). Also heterogeneity of the DMIPP uptake to MBF ratio, as an indicator of agreement, increased from 0.23 +/- 0.07 in normal to 0.46 +/- 0.19 in hypoperfused myocardium (p < 0.0001). Conclusion: DMIPP detects regionally hypoperfused myocardium, in which agreement between MBF and fatty acid uptake deteriorates. DMIPP uptake shows a different relationship with MBF in hypoperfused compared to normal myocardium. These observations suggest that DMIPP uptake may provide additional, unique information on regional myocardial ischemia.