Interregional differences in brain intracellular pH and water compartmentation during acute normoxic and hypoxic hypocapnia in the anesthetized dog

Abstract

Interregional differences in intracellular pH (pH i) in brain tissue, and its regulation following 1 and 5 h of respiratory alkalosis (with and without hypoxemia) were determined in N 2O anesthetized dogs. Two techniques for pH i estimation were used (T co 2 and 14C-DMO) and included corrections for measured extracellular fluid ( 35SO 4 2−) space (ECS). Cortical pH i by the two techniques agreed closely in control and in 3 of the 4 experimental conditions, suggesting: (a) our estimation of extracellular fluid (ECF) [HCO 3 −] from measured CSF [HCO 3 −] was a valid ssumption; and (b) our method had sufficient resolution to determine the magnitude of brain pH i regulation during respiratory acid-base disturbances. When moderate normoxic respiratory alkalosis (PaCO 2 ≈ 25 mm Hg) was imposed for 5 h, pH i (in most brain regions) was well regulated and always exceeded the incomplete regulation noted in bulk CSF. When moderate hypoxemia (PaO 2 ≈ 45 mm Hg) accompanied hypocapnia, pH i was more closely regulated during the early phase (1 h) of respiratory alkalosis. Increased levels of metabolic acids (especially lactic acid) were critical to brain pH i regulation during the initial hour of respiratory alkalosis and accounted for much of the independent effect of hypoxemia on pH i regulation. However, these metabolic acids remained unchanged as pH i was more completely regulated between 1 and 5 h of continued hypocapnia or hypoxic hypocapnia. This time-dependent tregulation of pH i may involve some regulatory role for changed transmembrane fluxes of H + and/or HCO 3 −. Significant interregional differences were observed in both pH i and in ECS; with tendencies toward more alkaline pH i and lower ECS in brain stem and white matter. With respiratory alkalosis ECS fell and intracellular fluid increased in both cortex and caudate nucleus, possibly reflecting an osmotic effect of increased metabolic acid levels or reduction in cell membrane ion pumping.