In an attempt to understand the mechanisms by which preischemic plasma glucose (pg) worsens neurologic and neuropathologic outcomes, we investigated the effect of moderate preischemic hyperglycemia (200 mg/dl < mean plasma glucose < 360 mg/dl) on postischemic energy metabolism, tissue intracellular pH (pHi) and tissue free intracellular pMg (= -log[Mg2+]) over a one week period after transient global cerebral ischemia in the rat. In vivo 31P nuclear magnetic resonance spectroscopy was performed prior to and daily up to 1 week (wk) in rats after 12 min of forebrain ischemia, induced by bicarotid occlusion concurrent with systemic hypotension. Preischemic plasma glucose significantly affected 1 wk postischemic survival (p = 0.05, Fisher's exact test). The temporal profile of the brain tissue pHi was significantly different (p < 0.03) between the moderate hyperglycemic (H-1wk, n = 7, mean pg = 266.0 +/- 47.3 mg/dl) and the normoglycemic (N-1wk, n = 8, mean pg = 91.2 +/- 23.7 mg/dl) ischemic animals over 1 wk. Postischemic tissue alkalosis was measured at 24 (p = < 0.006) and 48h (p = 0.001) postischemia in the N-1wk group. A single marginally significant (p = 0.011) mean pHi upshift was measured at 72h postischemia in the H-1wk group. The mean change in pHi at 24h postischemia from the baseline values in moderate hyperglycemic animals that survived only 48h after ischemia (H-48h, n = 6, mean pg = 298.8 +/- 70.1 mg/dl) was significantly lower (p = 0.02) than that of the N-1wk ischemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)