THE EFFECT OF MODERATE AND MARKED HYPERCAPNIA UPON THE ENERGY STATE AND UPON THE CYTOPLASMIC NADH/NAD⁺ RATIO OF THE RAT BRAIN

Abstract

The energy state of brain tissue was evaluated from the tissue concentrations of ATP, ADP and AMP and the cytoplasmic NADH/NAD + ratio from the tissue, CSF and blood concentrations of lactate and pyruvate, and from the intracellular pH', in rats exposed to carbon dioxide concentrations of 6 4 0 per cent. The hypercapnia had no significant effect on the energy state of the tissue. Hypercapnia of increasing severity gave rise to a progressive decrease in the pyruvate concentration ; the lactate concentration fell at low COz concentrations, but no further decrease was observed at COz concentrations greater than 20 per cent. There was a progressive rise in the intracellular lactate/pyruvate ratio at increasing COz concentrations, corresponding to the fall in intracellular pH, i.e. the calculated NADH/NAD+ ratios remained normal. It is therefore concluded that hypercapnia does not affect the cytoplasmic redox state.As REMARKED in a previous communication (SIESJO, FOLBERGROVA and MACMILLAN, 1972u), carbon dioxide has profound effects upon the function of the brain, ranging from seizure activity to anaesthesia. These effects raise the question whether or not CO, directly affects the energy metabolism of the tissue. Several reports demonstrate that moderate concentrations of CO, do not change the overall oxygen consumption of the human brain (KETY and SCHMIDT, 1948), and recent studies (SIESJO, FOLBER-GROVA and MESSETER, 19726; see also BAIN and KLEIN, 1949) have shown that such CO, concentrations are without effects on the energy state of the tissue, as evaluated from the tissue concentrations of ATP, ADP and AMP. However, since seizure activity or anaesthesia are elicited at much higher COz concentrations (WOODBURY and KARLER, 1960), it remains a possibility that the energy state of the tissue is affected first at extreme hypercapnia. In this connection it should be mentioned that CO, has been found to interfere with oxidative phosphorylation in liver mitochondria (FANESTIL, HASTINGS and MAHOWALD, 1963 ;KASBEKAR, 1966).We have recently reported that administration of about 11 % C 0 2 to rats for periods ranging from 15 min to 72 h was without effect upon the energy state of the tissue (SIESJO et al., 19726), but that acute hypercapnia (15 min-3 h) was associated with a small rise in the calculated cytoplasmic NADH/NAD+ ratio (MESSETER and SIESJO, 1971). In the present experiments, the energy state of the tissue and the cytoplasmic NADH/NAD+ ratio were studied in rats exposed to 6-40% CO, for 45 min.

Pyruvate Dehydrogenase Activity in the Rat Cerebral Cortex following Cerebral Ischemia

“…Since no ac tivation of PDHC with DCA was noted at 15 min of recirculation, the decreased levels of pyruvate could not be explained by a change in PDHC activ ity. A decrease in intracellular pH could account for the observed increase in lactate/pyruvate ratio, as was also found in hypercapnia (Folbergrova et al, 1972), and which is also indicated by the decreased PCr levels in the DCA + glucose-treated animals. However, the observed changes in intermediary metabolism apparently did not affect the PDHC ac tivity.…”

Chronic Dexamethasone Pretreatment Aggravates Ischemic Neuronal Necrosis

“…Samples of the parietal cortex and the hippocampus were dissected out from the brain at -22°C and assayed for metabolites and FFAs according to previously re ported methods (Folbergrova et al, 1972;Rehncrona et aI., 1982).…”

Bilirubin-Induced Changes in Brain Energy Metabolism after Osmotic Opening of the Blood-Brain Barrier

“…Samples were dissected and extracted with HCI-methano1 at -22°C and subsequently with perchloric acid at O°C, as previously described (26). Metabolites were measured with enzymatic fluorimetric techniques of Lowry and Passonneau (27). The adenylate energy charge (E.C.…”