GLUCOSE-METABOLISM DISTAL TO A CRITICAL CORONARY STENOSIS IN A CANINEMODEL OF LOW-FLOW MYOCARDIAL-ISCHEMIA

Myocardial regions perfused through a coronary stenosis may cease cont racting, but remain viable. Clinical observations suggest that increas ed glucose utilization may be an adaptive mechanism in such ''hibernat ing'' regions, In this study, we used a combination of C-13-NMR spectr oscopy, CC-MS analysis, and tissue biochemical measurements to track g lucose through intracellular metabolism in intact dogs infused with [1 -C-13]glucose during a 3-4-h period of acute ischemic hibernation, Dur ing low-now ischemia [3-C-13]alanine enrichment was higher, relative t o plasma [1-C-13]glucose enrichment, in ischemic than in nonischemic r egions of the heart, suggesting a greater contribution of exogenous gl ucose to glycolytic flux in the ischemic region (similar to 72 VS simi lar to 28%, P < 0.01) Both the fraction of glycogen synthase present i n the physiologically active glucose-6-phosphate-independent form (46 +/- 10 vs. 9 +/- 6%, P < 0.01) and the rare of incorporation of circul ating glucose into glycogen (94 +/- 25 vs, 20 +/- 15 nmol/gram/min, P < 0.01) were also greater in ischemic regions. Measurement of steady s tate [4-C-13]glutamate/[3-C-13]alanine enrichment ratios demonstrated that glucose-derived pyruvate supported 26-36% of total tricarboxylic acid cycle flux in all regions, however, indicating no preference for glucose over fat as an oxidative substrate in the ischemic myocardium, Thus during sustained regional low-now ischemia in vivo, the ischemic myocardium increases its utilization of exogenous glucose as a substr ate, Upregulation is restricted to cytosolic utilization pathways, how ever (glycolysis and glycogen synthesis), and fat continues to be the major source of mitochondrial oxidative substrate.