We tested the hypotheses that after complete cerebral ischemia, first, rate of recovery of ATP, phosphocreatine (PCr), and intracellular pH (pHi) varies with ischemic duration and second, rate of metabolic recovery is a more sensitive predictor of consequent electrophysiological deficit than steady-state metabolic recovery. With the use of transient intracranial hypertension in anesthetized dogs, ischemic duration was set for either 3, 12, or 30 min, which depressed somatosensory-evoked potential (SEP) recovery amplitude by 30, 59, and 88%, respectively. In contrast, ATP, PCr, and pHi, measured by 31P magnetic resonance spectroscopy, fully recovered. When ischemic duration was increased from 3 to 12 min, mean recovery time of ATP (6 min) remained rapid but that of pHi (12-28 min) was prolonged. After 30 min of ischemia, pHi recovery was not slowed further (25 min) but that of ATP was now markedly prolonged (36 min). PCr recovery time increased progressively with ischemic duration (5, 11, and 21 min, respectively) and correlated best with SEP recovery (r = 0.74). We conclude that the brain's ability to rapidly normalize pH is a sensitive predictor of electrophysiological recovery after short ischemia but that ATP regeneration becomes important with prolonged ischemia. PCr recovery rate was the best overall predictor, probably because it depends on both pHi and the ratio of ATP to ADP by the creatine kinase reaction.

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