THE INFLUENCE OF HYPOCAPNIA UPON INTRACELLULAR pH AND UPON SOME CARBOHYDRATE SUBSTRATES, AMINO ACIDS AND ORGANIC PHOSPHATES IN THE BRAIN

Abstract

Abstract— In order to evaluate the influence of hypocapnia upon the energy metabolism of the brain, lightly anaesthetized rats were hyperventilated to arterial CO2 tensions of 26, 15 and 10 mm Hg respectively, with subsequent measurements of intracellular pH and of tissue concentrations of carbohydrate substrates, amino acids and organic phosphates. At Pco1= 26 there was a moderate increase in the intracellular pH but when the Pco2 was reduced further to 10 mm Hg the intracellular pH returned to normal, or slightly subnormal, values. The reduction in PCo2 was accompanied by increased cerebral cortical concentrations of lactate, pyruvate, citrate, α‐ketoglutarate, malate and glutamate and by decreased aspartate concentrations. It is concluded that the accumulation of metabolic acids explains the normal value for intracellular pH at very low CO2 tensions. Previous results obtained in man indicate that there is an increased anaerobic production of lactic acid in the brain in extreme hypocapnia. At comparable CO2 tensions the present results showed a small fall in phosphocreatine and a small rise in ADP. However, since the ammonia concentrations were normal or decreased and since there was an increase in citrate, the results give no direct support to the hypothesis of an activation of phosphofructokinase. Since the cerebral venous Po2 was reduced to 20 mm Hg at an arterial CO2 tension of 10 mm Hg the accumulation of acids was probably secondary to tissue hypoxia. However, since there was no, or only a very small, increase in the calculated cytoplasmic NADH/NAD+ ratio, it appears less likely that acids accumulated due to lack of NAD+.

Cerebral physiological and metabolic effects of hyperventilation in the neonatal dog

“…Plum and Posner [19] and MacMillan and Siesjo [14] have argued that alkalosis may trigger increases in lactate.…”

“…Marked hypocarbia in the neonatal dog produces an elevated brain lactate level that may be related to changes in glycolytic rate rather than to tissue ischemia or hypoxia. [13,14, 191 that accompany prolonged hyperventilation in the adult human and laboratory animal have been ascribed to tissue ischemia resulting from marked vasoconstriction and to decreased oxygen availability during alkalosis (the Bohr effect). To determine whether prolonged hyperventilation may also lead to brain ischemia and elevation of brain lactate levels in the neonate, we measured CBF and levels of brain glucose, lactate, ATP, and phosphocreatine (PCr) after 90 minutes of hyperventilation in neonatal dogs.…”

Effects of hyperventilation on cerebral blood flow and brain tissue metabolism in normotensive and spontaneously hypertensive rats.

“…3 -*• 23,24 According to MacMillan and Siesjo's observations, 23 cerebral lac tate in rats was increased to 3.42 mM/kg at paC0 2 21.1 mmHg and 5.25 mM/kg at paC0 2 …”

Extra- and Intracellular pH in the Brain during Seizures and in the Recovery Period following the Arrest of Seizure Activity

“…An additional series was used to assess arterial and cerebro venous Pco2 during and following seizures. In these an imals, a burr hole was placed over the caudal part of the superior sagittal sinus to allow sampling of cerebrovenous blood (see Ponten and Siesj6, 1966;MacMillan and Siesj6, 1973). Yet another series was used for measuring pHe with double-barreled pH microelectrodes.…”