Spatial heterogeneity in fasting and insulin-stimulated ¹⁸F-2-deoxyglucose uptake in pigs with hibernating myocardium

Background - Previous studies of hibernating myocardium in the fasting state have shown regionally increased ¹⁸F-2-deoxyglucose (FDG) uptake with a marked transmural gradient. We hypothesized that this adaptation to chronic ischemia might be associated with altered maximal FDG uptake. Methods and Results - Pigs were instrumented with a 1.5-mm proximal left anterior descending artery (LAD) stenosis. Studies were conducted 106±4 days later on anesthetized animals with complete LAD occlusion and anteroapical dysfunction. In fasting animals (n=9), FDG uptake in dysfunctional LAD regions was 2-fold higher than in normally perfused myocardium (7.9±1.2 versus 4.0±0.5 μmol · min^-1 · 100 g^-1, P<0.05), with a pronounced transmural gradient (endocardial/epicardial ratio 2.56±0.19 versus 1.25±0.03, P<0.05). Euglycemic, hyperinsulinemic clamp (insulin clamp, n=8) produced a 5- to 9-fold increase in FDG uptake, but there was no longer a regional difference in accumulation (LAD, 37.8±4.2 versus normal, 36.4±5.1 μmol · min^-1 · 100 g^-1, P=NS) and the transmural distribution was uniform. FDG uptake in the fasting state varied inversely with coronary flow during vasodilation. In contrast, during insulin clamp there was no relation between FDG uptake and vasodilated flow, resulting in a reduced spatial heterogeneity in individual samples (relative dispersion=SD/mean; fasting, 52±5% versus insulin, 24±2%, P<0.05). Conclusions - In the fasting state, FDG uptake in pigs with hibernating myocardium was heterogeneous and was increased in dysfunctional regions with a marked transmural gradient and high spatial heterogeneity. In contrast, FDG uptake was more homogeneously distributed during insulin clamp with (1) uptake in dysfunctional myocardium similar to remote normal regions, (2) uniform transmural distribution, and (3) reduced spatial heterogeneity.