Stimulated glucose uptake in the ischemic border zone: Its dependence on glucose uptake in the normally perfused area

During acute regional myocardial ischemia, a 'border zone' exists where the spatial distributions of blood flow and substrate uptake show gradual changes. We investigated the relationship between blood flow and glucose uptake in the border zone during acute regional ischemia. Methods: Newly developed quantitative autoradiography using imaging plates and two long- lived radioisotopes was applied to rat hearts subjected to 30 min of left coronary artery occlusion. Blood flow, glucose uptake and fatty acid uptake was assessed with 4-[N-methyl-¹⁴C]iodoantipyrine, 2-deoxy-D-[1-³H]glucose (³H-DG) and β-methyl[1-¹⁴C]heptadecanoic acid (¹⁴C-BMHDA), respectively. Results: In rats showing ³H-DG uptake in the normally perfused area (Norm) of 254 ± 96 Bq/mg (high-DG) and 56 ± 20 Bq/mg (low-DG) (n = 4 for each), ³H-DG uptake in the border zone was 148 ± 52 Bq/mg and 58 ± 15 Bq/mg (p<0.05 high- versus low-DG), respectively. The relationship between blood flow and ³H-DG uptake in the border zone was altered by the different ³H-DG uptake levels in Norm. In high-DG, ³H-DG uptake in the border zone was reduced significantly according to the decrease in the percentage of blood flow. However, in low-DG, no significant differences in ³H-DG uptake were found among the regions in the border zone with different levels of the percentage of blood flow, except in the region with 10%-19% of the percentage of blood flow. In the border zone, the percentage of ³H-DG uptake per unit blood flow normalized to that in Norm increased according to the decrease in the percentage of blood flow, and this increase was steeper in low-DG than in high-DG (p<0.0005). The percentage of ¹⁴C-BMHDA uptake was lower than the percentage of ³H-DG uptake (27 ± 3% versus 78 ± 18% of that in Norm, p<0.0005) in the peripheral ischemic area. Conclusion: The relationship between blood flow and glucose uptake in the ischemic border zone was altered by the different glucose uptake levels in Norm. Glucose uptake in the border zone was higher in rats with higher glucose uptake levels in Norm, suggesting that glucose uptake in the border zone stimulated by ischemia can be accelerated still more by humoral factors.