Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia

Myocardial regions perfused through a coronary stenosis may cease contracting, but remain viable. Clinical observations suggest that increased glucose utilization may be an adaptive mechanism in such ''hibernating'' regions, In this study, we used a combination of C-13-NMR spectroscopy, CC-MS analysis, and tissue biochemical measurements to track glucose through intracellular metabolism in intact dogs infused with [1-C-13]glucose during a 3-4-h period of acute ischemic hibernation, During low-now ischemia [3-C-13]alanine enrichment was higher, relative to plasma [1-C-13]glucose enrichment, in ischemic than in nonischemic regions of the heart, suggesting a greater contribution of exogenous glucose to glycolytic flux in the ischemic region (similar to 72 VS similar to 28%, P < 0.01) Both the fraction of glycogen synthase present in the physiologically active glucose-6-phosphate-independent form (46 +/- 10 vs. 9 +/- 6%, P < 0.01) and the rare of incorporation of circulating glucose into glycogen (94 +/- 25 vs, 20 +/- 15 nmol/gram/min, P < 0.01) were also greater in ischemic regions. Measurement of steady state [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 substrate, Upregulation is restricted to cytosolic utilization pathways, however (glycolysis and glycogen synthesis), and fat continues to be the major source of mitochondrial oxidative substrate.