Arterial acid--base changes and brain energy metabolism in unanaesthetized rats in mild hypoxia.

Abstract

Abstract The behaviour of acid-base balance in the blood and of glycolytic pathway intermediates (glucose, glucose 6-phosphate, pyruvate, lactate, ATP, ADP, AMP and phosphocreatine) in the brains of rats was studied in animals breathing 7.5% O 2 in N 2 for 2 h. In the blood, a progressive non-respiratory acidosis reduced the initial shift of pH towards the alkaline direction; however, the concomitant decrease of P a,C0 2 maintained its value still above control values. The accumulation of lactate was followed by a rise in pyruvate concentration and resulted in relatively stable values for lactate excess and lactate/pyruvate ratios. The observed fall in blood pressure probably reflected the cardiac response to hypoxia and did not exceed 20 mmHg during 2 h of experiment. This decrease, however, was probably not limiting for brain perfusion, stimulated by hypoxia, since we observed no failure of energy metabolism in the brain. The triggering factors for the activation of glycolysis in the brain, under circumstances of unchanged ATP, ADP and AMP concentrations, are difficult to define. In all probability the results reflect an initial activation of glycolysis at the phosphofructokinase step and a further partial inhibition of primarily accelerated flux at the hexokinase level, with subsequent limitation of glucose influx. Such dynamic changes in regulatory mechanisms of glycolysis resulted in maintaining stable lactate/pyruvate ratios during 2 h of hypoxia, and suggest the acquirement of a new steady state of the glycolytic rate in conditions of long-lasting hypoxia.