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 persist ing postischemic acidosis or the extent of acidosis would affect metab olic recovery following an ischemic event. Intracellular pH (pH(i)), a denosine triphosphate, phosphocreatine, and lactate levels were measur ed in the cerebral cortex during the early stages of reperfusion, foll owing either 5 or 10 minutes of global ischemia in both normo- and hyp erglycemic gerbils. A total of 130 gerbils were injected with a soluti on containing 1.5 mi Neutral Red (1%) (+/- 2.5 gm/kg glucose); 30 minu tes 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 afte r reperfusion; they were sectioned and the block face was photographed to determine the pH(i) by using Neutral Red histophotometry. At the c onclusion of the ischemia, the pH(i) in all groups had decreased signi ficantly from a control value of 7.05 +/- 0.03 (mean +/- standard erro r 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, respec tively. Hyperglycemic brains were more acidotic; values fell to 6.57 /- 0.10 and 6.52 +/- 0.24 after 5 and 10 minutes of ischemia, respecti vely. Lactate levels were approximately fivefold greater than those of control tissue in normoglycemic brains, while lactate levels in hyper glycemic brains were increased eightfold. The adenosine triphosphate a nd phosphocreatine levels were depleted at the end of ischemia in all groups. After 2 minutes of renew activity, the pH(i) levels in both no rmo- and hyperglycemic brains were restored to those of control values in the 5-minute ischemic group, while the pH(i) levels remained signi ficantly depressed in the 10-minute ischemic group. Restoration of hig h-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, ther e was complete recovery of high-energy phosphates by 2 minutes of refl ow activity following 5 minutes of ischemia. Extending the ischemic pe riod to 10 minutes in hyperglycemic brains slowed the rate of metaboli c recovery to that observed in normoglycemic brains. The results indic ate that the reflow period permits the rapid restoration of pH(i) leve ls substantially before the normalization of primary energetic compoun ds. In addition, hyperglycemia appears to be transiently beneficial in the initial critical moments of renew activity following short-term i schemia, but provides no immediate benefit in terms of energy stores w hen ischemic duration is prolonged. The lack of a prolonged benefit to energy status and the well-known deleterious effects of increased aci dosis support the concept that hyperglycemic conditions should be avoi ded during temporary ischemia.