Changes in the cerebral metabolism induced by hyperventilation at different blood glucose levels.

Abstract

Abstract—In order to study cerebral metabolism in hypocapnia, lightly anaesthetized rats were hyperventilated to PaCO2 about 15 mm Hg for 1, 2, 5 and 30min, the brain was frozen in situ, and cortical concentrations of organic phosphates, glycolytic and citric acid cycle metabolites, and amino acids were measured. In separate experiments, animals were made hypoglycaemic prior to induction of hypocapnia. Measurements of arteriovenous differences for oxygen and glucose indicated an increased glycolytic flux and the pattern of changes in glycolytic intermediates after 1 min suggested that this was due to an activation of the phosphofructokinase step.The pool size of citric acid cycle intermediates gradually increased with time of hypocapnia. This increase was, as in hypoxic hypoxia, related to the accumulation of pyruvate, probably via its effect on the alanine aminotransferase reaction and on the rate of CO2 fixation at the pyruvate carboxylase step. In hypoglycaemic, hypocapnic animals, in which the production of pyruvate was limited, the increase in pool size did not occur. It is suggested that the pyruvate concentration determines the net flux at the CO2 fixation step and thereby the direction of net flux of carbon skeletons between the citric acid cycle and the glycolytic chain. The changes in amino acids (glutamate, glutamine, alanine, GABA and aspartate) with time of hypocapnia were also similar to those occurring in hypoxic hypoxia. Thus, there was an increase in alanine concentration and a shift in aspartate aminotransferase reaction with increase in glutamate and fall in aspartate. It is suggested that the increase in alanine was secondary to a rise in pyruvate concentration, and that the shift in the aspartate aminotransferase reaction was due to reduction of the malate dehydrogenase system. This interpretation is supported by the fact that hypoglycaemia, by preventing a rise in pyruvate concentration and a reduction in the cytoplasmic redox system, also prevented the changes in amino acids.