Glucose metabolism during ischemia due to excessive oxygen demand or altered coronary flow in the isolated arterially perfused rabbit septum.

Abstract

The isolated arterially perfused interventricular rabbit septum was adapted for the study of glucose metabolism during ischemia produced by either increased oxygen demand or altered coronary flow. The septum perfused at 1.5 ml/min and stimulated at a rate of 72/min at 37 C was shown to be a low work preparation in which glucose utilization, lactate production, oxygen consumption, and developed tension were stable for at least 90 minutes. The metabolic and functional responses of the septum were evaluated during nonnoxic 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 nonnoxic increased work, glucose utilization increased by 115 26% (KM) over control, while oxygen consumption increased by 100 11%, lactate production by 13 9%, and developed tension by 45 8%. Tigsue glycogen, lactate, and lactate:pyruvate ratios were unchanged compared to control. During demand-induced ischemia, glucose utilization increased by 116 24%, while oxygen consumption increased only by 29 7%, lactate production rose by 106 16%, and developed tension declined by 20 4%. Tissue glycogen content was significantly decreased and tissue lactate and lactaterpyruvate ratios were significantly increased during demand-induced ischemia compared to both control and nonnoxic increased work. These results are consistent with accelerated glucose oxidation during nonnoxic 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 oxygen consumption decreased by 80 8% and 74 2%, respectively. The results of this study suggest that 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 oxygen demand. Ore Res 49: 640-648, 1981 DURING myocardial ischemia there is a mismatch between oxygen supply and demand. Glucose metabolism during ischemia is dependent on residual perfusion for washout of the metabolic end products, lactate and hydrogen ion (Rovetto etal., 1975). This finding expains the observation that glucose uptake and metabolism accelerate if the myocardium is made hypoxic by perfusion with oxygenfree perfusate at maintained flow rates, but does not accelerate or even declines if the myocardium is made hypoxic by decreasing flow rates (Rovetto et al.,