High resolution analysis reveals a temporally stable, patchy pattern of perfusion in the left ventricular free wall, that is associated with spatial heterogeneity of energy turnover. Low flow areas (LowF) are also characterized by increased expression of glycolytic enzymes and enhanced fatty acid content. This suggested distinct metabolic phenotypes in the heart.

In comparison to canine High flow samples (HighF), lipid profile analysis of LowF (300 ml, <60 vs. >140% of mean) revealed an elevated triglyceride content (+212%, p<0.01), but no change in 7 other lipids identified. In LowF, mRNA expression of the transcription factor PPARa was reduced to 1/4 (n=6 each, p<0.001) and the same was true for key enzymes of lipid metabolism: CPT-1, transfering activated fatty acids through the mitochondrial membrane, was decreased to 1/3, possibly explaining the increased triglyceride content. Fatty acid translocase was reduced by 1/2 and FABP and lipoproteinlipase by 1/3 (p<0.05 ? 0.001). Conversely, HighF demonstrated enhanced mRNA expression of these enzymes. Thus, within the apparently homogeneous LV wall, substantial differences in local perfusion and metabolic profile exist. The downregulation of fatty acid oxidation in LowF, resembling changes in severe heart failure, will further reduce O2 consumption in these regions.