Chronic myocardial ischemia and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) uptake were studied with positron emission tomography in 12 swine instrumented with an external constrictor on the left anterior descending coronary artery (LAD). Serial changes in function (by echocardiography), blood flow (with H215O) and FDG were determined weekly. At 1 wk, function was normal and FDG uptake in the LAD and non-LAD regions was 0.43 +/- 0.12 and 0.45 +/- 0.11 mumol. min-1.g-1, respectively (not significant). At approximately 5 wk, LAD wall thickening decreased to 18 +/- 5 from 27 +/- 8% (P < 0.05), whereas LAD and non-LAD blood flows were 0.68 +/- 0.28 and 1.03 +/- 0.25 ml.min-1.g-1, respectively (P < 0.05). At that time, FDG uptake in LAD and non-LAD regions was 0.60 +/- 0.43 and 0.49 +/- 0.30 mumol.min-1.g-1, respectively (P < 0.05). By the use of transmural biopsies (n = 6), ATP and creatine phosphate in the LAD region were 3.62 +/- 0.73 and 5.91 +/- 1.44 mumol/g wet wt, respectively, and neither differed from values in remote regions. In this model of chronic ischemia, hypoperfused dysfunctional regions were characterized by enhanced glucose uptake and preserved bioenergetics. This supports the concept that the myocardium adapts to chronic ischemia.