GLUCOSE-METABOLISM DURING ISCHEMIA DUE TO EXCESSIVE OXYGEN-DEMAND OR ALTERED CORONARY FLOW IN THE ISOLATED ARTERIALLY PERFUSED RABBIT SEPTUM

The isolated arterially perfused interventricular rabbit septum was adapted for the study of glucose metabolism during ischemia produced by either increased O2 demand or altered coronary flow. The septum perfused at 1.5 ml/min and stimulated at a rate of 72/min at 37.degree. C was a low work preparation in which glucose utilization, lactate production, O2 consumption and developed tension were stable for at least 90 min. The metabolic and functional responses of the septum were evaluated during normoxic increased work produced by introducing a paired stimulus at 90/min and increasing flow to 3.5 ml/min, during demand-induced ischemia produced by introducing a paired stimulus at 90/min and maintaining flow at 1.5 ml/min, and during low flow ischemia produced by decreasing flow and maintaining stimulus rate constant at 72/min. During normoxic increased work, glucose utilization increased by 115 .+-. 26% (.+-. SEM [standard error of the mean]) over control, while O2 consumption increased by 100 .+-. 11%, lactate production by 13 .+-. 9% and developed tension by 45 .+-. 8%. Tissue glycogen, lactate and lactate:pyruvate ratios were unchanged compared to control. During demand-induced ischemia, glucose utilization increased by 115 .+-. 24%, while O2 consumption increased only by 29 .+-. 7%, lactate production rose by 106 .+-. 19% and developed tension declined by 20 .+-. 4%. Tissue glycogen content was significantly decreased and tissue lactate and lactate:pyruvate ratios were significantly increased during demand-induced ischemia compared to both control and normoxic increased work. These results are consistent with accelerated glucose oxidation during normoxic increased work and accelerated anaerobic glycolysis during demand-induced ischemia. During severe low flow ischemia, glucose utilization declined by 44 .+-. 8% while developed tension and O2 consumption decreased by 80 .+-. 8% and 74 .+-. 2%, respectively. Apparently the dependence of glucose metabolism in ischemia on residual perfusion for washout of metabolic end products is also observed when ischemia is produced by excessive O2 demand.