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We studied the intracellular pH in rat cerebral cortex of rats subjected to reversible total cerebral ischemia by cardiac arrest and resuscitation. Brain acidoses was more pronounced during ischemia in hyperglycemic rats (6.21 +/- 0.14) than in normoglycemic rats (6.56 +/- 0.07). Brain tissue lactate accumulated proportionally. Nevertheless, within 5 min of reperfusion, pHi in both normoglycemic and hyperglycemic groups had recovered to baseline levels, i.e. near 7.1-7.2, despite the fact that lactate concentrations were still elevated. These results demonstrate a rapid reversal of ischemic acidosis during recovery from 10 min of cardiac arrest, and suggest that acidosis, per se, may not be responsible for neuronal damage following cardiac arrest and resuscitation, even in hyperglycemic conditions.

Tissue acidosis is an important determinant of cell viability following cerebral ischemia. Because of the heterogeneity of tissue response to metabolic stress, a method for measuring intracellular pH (pHi) that preserves spatial information would be desirable. Histophotometry of the pH indicator dye Neutral red offers such a possibility. The purpose of our study was to determine the distribution of pHi following complete irreversible ischemia and show the correlation of mean pHi measured by Neutral red and [31P]NMR in the same brain. Three rats were studied in the anesthetized state. A pHi range was obtained by total cerebral ischemia at various pre-arrest plasma glucose concentrations. The data show that mean pHi calculated by Neutral red was strongly correlated to pHi determined from [31P]NMR (slope: 0.99 +/- 0.08; P less than 0.001, r2 = 0.96). Within each brain, 80-110 discrete samples were analyzed by histophotometry. The pHi distribution of those samples broadened in those rat brains with greater acidosis, suggesting a heterogeneity of response by the tissue to ischemia and the presence of multiple pHi pools. Our results demonstrate the need to use methods which maintain spatial resolution such as is available with histophotometry.