Changes in Extra- and Intracellular pH in the Brain during and following Ischemia in Hyperglycemic and in Moderately Hypoglycemic Rats

Incomplete forebrain ischemia of 15-min duration was induced in rats made hyperglycemic or moderately hypoglycemic prior to ischemia. Tissue CO 2 tension, CO 2 content, labile tissue metabolites, and extracellular pH (pH e ) were measured, and intracellular pH (pH i ) was derived by calculation on the assumption that cerebral intracellular fluids can be lumped into one space. In hypoglycemic animals, mean tissue lactate content increased from 2 to 10 μmol g −1 . Tissue CO 2 content was virtually unchanged and the CO 2 tension increased from ∼50 to ∼145 mm Hg. In hyperglycemic animals, tissue lactate content rose to 20 μmol g −1 , and the CO 2 content decreased by 25%, demonstrating that some CO 2 was lost to the blood supplied by the remaining perfusion. Accordingly, tissue CO 2 tension did not rise above 200 mm Hg. pH e was reduced in proportion to the amount of lactate accumulated, the values obtained in hypo- and hyperglycemic animals showing relatively little scatter (6.76 ± 0.03 and 6.25 ± 0.04, respectively). In hypoglycemic animals the extracellular HCO − 3 concentration was virtually unchanged, demonstrating that any influx of lactic acid from the cells must have been accompanied by H + efflux and/or HCO − 3 influx via independent routes. In hyperglycemic animals HCO − 3 e fell by >10 μmol ml −1 . In both groups HCO − 3 e was reduced during the first 5 min of recovery. Recovery of pH e was slower in hyper- than in hypoglycemic animals. During ischemia calculated pH i fell to 6.37 ± 0.04 and 5.95 ± 0.06 in hypo- and hyperglycemic animals, respectively. Differences in pH i were maintained for the first 15 min of recovery, but in both hypo- and hyperglycemic animals pH i had normalized after 30 min. It is concluded that preischemic hyperglycemia leads to a more pronounced intra- and extracellular acidosis than normo- and hypoglycemia, an acidosis that also resolves more slowly during recirculation.