Pelligrino D A, Musch T I, Dempsey J A
Brain Res. 1981 Jun 15;214(2):387-404. doi: 10.1016/0006-8993(81)91202-6.
Interregional differences in intracellular pH (pHi) in brain tissue, and its regulation following 1 and 5 h of respiratory alkalosis (with and without hypoxemia) were determined in N2O anesthetized dogs. Two techniques for pHi estimation were used (TCO2 and 14C-DMO) and included corrections for measured extracellular fluid (35SO4(2-)) space (ECS). Cortical pHi by the two techniques agreed closely in control and in 3 of the 4 experimental conditions, suggesting: (a) our estimation of extracellular fluid (ECF) [HCO3-] from measured CSF [HCO3-] was a valid assumption; and (b) our method had sufficient resolution to determine the magnitude of brain pHi regulation during respiratory acid-base disturbances. When moderate normoxic respiratory alkalosis (PaCO2 approximately 25 mm Hg) was imposed for 5 h, pHi (in most brain regions) was well regulated and always exceeded the incomplete regulation noted in bulk CSF. When moderate hypoxemia (PaO2 approximately 45 mm Hg) accompanied hypocapnia, pHi 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 pHi regulation during the initial hour of respiratory alkalosis and accounted for much of the independent effect of hypoxemia on pHi regulation. However, these metabolic acids remained unchanged as pHi was more completely regulated between 1 and 5 h of continued hypocapnia or hypoxic hypocapnia. This time-dependent regulation of pHi may involve some regulatory role for changed transmembrane fluxes of H+ and/or HCO3-. Significant interregional differences were observed in both pHi and in ECS; with tendencies toward more alkaline pHi 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.
在氧化亚氮麻醉的犬中，测定了脑组织细胞内pH（pHi）的区域间差异，以及呼吸性碱中毒（伴有和不伴有低氧血症）1小时和5小时后的调节情况。使用了两种pHi估计技术（总二氧化碳（TCO2）和14C-二甲基异脲（14C-DMO）），并对测量的细胞外液（35SO4(2-)）空间（ECS）进行了校正。在对照和4种实验条件中的3种条件下，两种技术测得的皮质pHi非常接近，这表明：（a）我们根据测得的脑脊液[HCO3-]估算细胞外液（ECF）[HCO3-]是一个有效的假设；（b）我们的方法有足够的分辨率来确定呼吸性酸碱紊乱期间脑pHi调节的幅度。当进行5小时的中度常氧性呼吸性碱中毒（动脉血二氧化碳分压（PaCO2）约为25 mmHg）时，pHi（在大多数脑区）调节良好，且总是超过大量脑脊液中观察到的不完全调节。当中度低氧血症（动脉血氧分压（PaO2）约为45 mmHg）伴随低碳酸血症时，在呼吸性碱中毒的早期阶段（1小时）pHi调节更为紧密。代谢酸（尤其是乳酸）水平的升高在呼吸性碱中毒最初1小时对脑pHi调节至关重要，并且是低氧血症对pHi调节产生独立影响的主要原因。然而，随着持续低碳酸血症或低氧性低碳酸血症在1至5小时内pHi得到更完全的调节，这些代谢酸保持不变。pHi的这种时间依赖性调节可能涉及H+和/或HCO3-跨膜通量变化的某种调节作用。在pHi和ECS中均观察到显著的区域间差异；脑干和白质中pHi有更偏碱性的趋势，ECS较低。发生呼吸性碱中毒时，皮质和尾状核中的ECS下降，细胞内液增加，这可能反映了代谢酸水平升高或细胞膜离子泵减少的渗透作用。
