EARLY REVERSAL OF ACIDOSIS AND METABOLIC RECOVERY FOLLOWING ISCHEMIA

Tissue acidosis is believed to be a key element in ischemic injury of neural tissue. The goal of this study was to determine whether persisting postischemic acidosis or the extent of acidosis would affect metabolic recovery following an ischemic event. Intracellular pH (pH(i)), adenosine triphosphate, phosphocreatine, and lactate levels were measured in the cerebral cortex during the early stages of reperfusion, following either 5 or 10 minutes of global ischemia in both normo- and hyperglycemic gerbils. A total of 130 gerbils were injected with a solution containing 1.5 mi Neutral Red (1%) (+/- 2.5 gm/kg glucose); 30 minutes later, the gerbils were placed under halothane anesthesia, and the carotid arteries were occluded for either 5 or 10 minutes. The brains were frozen in liquid nitrogen at 0, 15, 30, 60, and 120 seconds after reperfusion; they were sectioned and the block face was photographed to determine the pH(i) by using Neutral Red histophotometry. At the conclusion of the ischemia, the pH(i) in all groups had decreased significantly from a control value of 7.05 +/- 0.03 (mean +/- standard error of the mean). In normoglycemic brains, the pH(i) values fell to 6.71 +/- 0.04 and 6.68 +/- 0.11 after 5 and 10 minutes of ischemia, respectively. Hyperglycemic brains were more acidotic; values fell to 6.57 +/- 0.10 and 6.52 +/- 0.24 after 5 and 10 minutes of ischemia, respectively. Lactate levels were approximately fivefold greater than those of control tissue in normoglycemic brains, while lactate levels in hyperglycemic brains were increased eightfold. The adenosine triphosphate and phosphocreatine levels were depleted at the end of ischemia in all groups. After 2 minutes of renew activity, the pH(i) levels in both normo- and hyperglycemic brains were restored to those of control values in the 5-minute ischemic group, while the pH(i) levels remained significantly depressed in the 10-minute ischemic group. Restoration of high-energy phosphates was similar in normoglycemic brains regardless of ischemic duration, recovering to only 20% of the restoration obtained in control tissue at 2 minutes. In hyperglycemic brains, however, there was complete recovery of high-energy phosphates by 2 minutes of reflow activity following 5 minutes of ischemia. Extending the ischemic period to 10 minutes in hyperglycemic brains slowed the rate of metabolic recovery to that observed in normoglycemic brains. The results indicate that the reflow period permits the rapid restoration of pH(i) levels substantially before the normalization of primary energetic compounds. In addition, hyperglycemia appears to be transiently beneficial in the initial critical moments of renew activity following short-term ischemia, but provides no immediate benefit in terms of energy stores when ischemic duration is prolonged. The lack of a prolonged benefit to energy status and the well-known deleterious effects of increased acidosis support the concept that hyperglycemic conditions should be avoided during temporary ischemia.