The effects of elevated
glucose on cardiac function during
hypoxia were investigated in isolated arterially perfused rabbit interventricular septa. Rest tension, developed tension, intracellular potential, 42K+ efflux,
lactate production, exogenous
glucose utilization, and tissue high-energy
phosphate levels were measured during a 50-min period of
hypoxia with 4, 5, or 50 mM
glucose present (isosmotically balanced with
sucrose) and during reoxygenation for 60 min with perfusate containing 5 mM
glucose/45 mM
sucrose. At physiologic (4 or 5 mM) and supraphysiologic
glucose (50 mM),
lactate production and high-energy
phosphate levels during
hypoxia were equally well maintained, yet cardiac dysfunction was markedly attenuated by 50 mM
glucose. Despite identical rates of total glycolytic flux, exogenous
glucose utilization was enhanced by 50 mM
glucose so that tissue
glycogen levels remained normal during
hypoxia, whereas
glycogen became depleted with 4 or 5 mM
glucose present during
hypoxia. Most of the beneficial effects of 50 mM
glucose occurred during the first 25 min of
hypoxia. Prior
glycogen depletion had no deleterious effects during
hypoxia with 50 mM
glucose present, but exacerbated cardiac dysfunction during
hypoxia with 5 mM
glucose present. These findings indicate that enhanced utilization of exogenous
glucose improved cardiac function during
hypoxia without increasing total glycolytic flux or tissue high-energy
phosphate levels, suggesting a novel cardioprotective mechanism.