Cerebral metabolic profile, selective neuron loss, and survival of acute and chronic hyperglycemic rats following cardiac arrest and resuscitation

Cortical metabolites and regional cerebral intracellular pH (pH(i)) were me asured in normoglycemic (NM), acute hyperglycemic (AH), and chronic hypergl ycemic (CH, 2, week duration, streptozotocin-induced) Wistar rat brains dur ing cardiac arrest and resuscitation. During total ischemia in AH and CH ra ts (plasma glucose similar to 30 mM), cortical ATP, PCr, glucose, and glyco gen all fell significantly as expected. Lactate levels increased dramatical ly in association with a concomitant intracellular acidosis. Although lacta te reached higher concentrations in AH and CH than Nhl, pH(i), was signific antly lower only in the AH group. With 5 min of reperfusion, all groups rec overed to near baseline in all variables, though lactate remained elevated. In a separate aspect of the study, animals from each experimental group we re allowed to recover for 4 days following resuscitation, with outcome bein g gauged by mortality rate and hippocampal CAI neuron counts. Nh? survival rate was significantly better than AH and CH. In particular, no CH rats sur vived for 4 days despite rapid initial recovery. After 4 days, the AH group had suffered significantly greater CA1 neuron loss than the NM rats. In su mmary, our research identified differences in intra-ischemic acid-base stat us in the two hyperglycemic groups, suggesting that chronic hyperglycemia m ay alter the brain's buffering capacity. These observations may account for differences between acutely and chronically hyperglycemic subjects regardi ng outcome, and they suggest that factors other than hydrogen ion productio n during ischemia are responsible for modulating outcome. (C) 1999 Elsevier Science B.V. All rights reserved.