PATTERNS OF CHANGES IN BRAIN CARBOHYDRATE METABOLITES, AMINO ACIDS AND ORGANIC PHOSPHATES AT INCREASED CARBON DIOXIDE TENSIONS

Abstract

—In order to study the time course of changes in cerebral metabolites in hypercapnia, anaesthetized and artificially ventilated rats were exposed to 11% CO₂ for 5, 15, 45, 90 and 180 min. In addition, the effect of anaesthetic levels of carbon dioxide was studied by exposing animals to 30 and 50% CO₂ for 45 min. In none of the groups were there significant changes in ATP, ADP or AMP, and a normal energy state was therefore obtained even in short‐lasting hypercapnia, and at anaesthetic CO₂ concentrations (50% CO₂). In the group exposed to 11% CO₂ for 5 min there was a fall in glycogen but normalization occurred when the hypercapnia was prolonged. There were no changes in fructose 1,6‐diphosphate, dihydroxyacetone phosphate or 3‐phosphoglycerate but decreases in pyruvate, lactate, citrate, α‐oxoglutarate, malate and glutamate at all exposure times. With 30 and 50% CO₂ glucose 6‐phosphate accumulated. The results do not support the view that the depletion of pyruvate and of citric acid cycle intermediates is caused by H⁺‐inhibition of rate‐limiting enzymatic steps like the phosphofructokinase reaction.The glutamate concentration fell progressively during exposure to 11% CO₂. In the 5 and 15 min groups aspartate increased significantly indicating that the initial loss of glutamate was partly due to transamination to aspartate. With prolonged hypercapnia there was a secondary fall in aspartate to subnormal values. At 45 min and thereafter the glutamine concentration increased significantly. However, the sum of glutamate, aspartate and glutamine fell progressively after the initial 5 min period.Hypercapnia gave rise to similar increases in the lactate/pyruvate and malate/oxaloacetate ratios, and since the calculated NADH/NAD⁺ ratios remained close to normal in all groups, the results indicate that pH‐dependent shifts occurred in the lactate and malate dehydrogenase equilibria.