Metabolic acids and [H+] regulation in brain tissue during acclimatization to chronic hypoxia.
Ventilatory acclimatization, arterial acid-base status, brain stem and cortex metabolic acids, and high-energy phosphates were determined in rats during 2-h to 7-days exposure to two levels of hypoxia (O2 inspiratory pressure 75 and 58 Torr), and upon acute restoration of normoxia. Brain lactate concentrations increased during acute exposure to both moderate hypoxia (+52% in cortex and +61% in stem) and severe hypoxia (+211% in cortex and +163% in stem), and during chronic hypoxia remained unchanged or decreased, respectively, as hyperventilation progressed and arterial O2 content rose. Restoration of normoxia after chronic hypoxic exposure resulted in continued hyperventilation and elevated lactate concentrations. Brain intracellular pH was unchanged throughout moderate hypoxia and during severe hypoxia, became acid during acute exposure, but was completely compensated after 72 h of continued hypoxia. Preventing the hypocapnia (via increased inspiratory fraction of CO2) during acute hypoxia or restoring normocapnia during posthypoxic normoxia revealed the effects of hypocapnia independently of hypoxemia. Hypocapnia accounted for all of the changes in brain lactate concentration during moderate hypoxia but only 40-60% of the lactate changes during severe hypoxia. We speculate that the observed changes in plasma and brain tissue metabolic acids and in plasma [HCO-3] would acidify cerebral interstitial fluid (ISF) in chronic hypoxia; however, the time course of this change in ISF acid-base status would be quite different between the two levels of hypoxia and uncorrelated with the patterns of ventilatory acclimatization.
D000136:Acid-Base Equilibrium; D000222:Adaptation, Physiological; D000818:Animals; D001158:Arteries; D001921:Brain / Q000503:physiopathology*; D001923:Brain Chemistry; D002245:Carbon Dioxide / Q000097:blood; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000097:blood; D010710:Phosphates / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D002245:Carbon Dioxide; D010100:Oxygen