Influence of Lactate Accumulation on Calcium Content of Ischemic and Postischemic Brain

Abstract

Summary: In this study, the cerebral hemisphere content of calcium as well as selected parameters of oxidative metabolism and electro physiological function were as sessed in normoglycemic and hyperglycemic rats that were exposed to ischemia produced by electrocautery of the vertebral arteries and reversible occlusion of the ca rotid arteries. In hyperglycemic animals, 0.5 h of isch emia was associated with large accumulations of lactate (27 mmol!kg), whereas normoglycemic animals showed lesser lactate accumulation (17 mmollkg). At this sam pling time (0.5 h of ischemia), both groups of ischemic animals showed tissue calcium contents that were un changed from preischemic control levels. In normoglyce mic animals, release of the carotid clamps and recircula tion for 1.5-24 h was associated with normalization of Animals administered glucose prior to the induc tion of cerebral ischemia show a greater degree of metabolic, electrophysiologic, and histologic dam age when compared to fasted animals exposed to an equivalent degree and duration of ischemia (Myers and Yamaguchi, 1976; Welsh et aI. , 1980; Rehn crona et aI. , 1981; Kalimo et aI. , 1981; Pulsinelli et aI., 1982). It has also been established that these indices of tissue damage are best correlated to the excessive accumulation of lactic acid in the brain of the glucose-loaded animal (Myers, 1979). Although it has been shown that direct injection of N a lactate, sufficient to lower brain pH to about 5, can cause neuronal damage and astrocytic swelling (Petito et aI., 1987), the precise mechanism by which exces sive lactic acidosis accentuates ischemic brain dam age is as yet undefined. The possibilities discussed 640lactate, ATP and phosphocreatine, clinical behavior, and EEG. During this 24 h of recirculation, cerebral calcium levels showed no changes. Hyperglycemic ischemic ani mals recirculated for 1.5-24 h showed a persistent lactic acidosis, depressed ATP and phosphocreatine, gross EEG abnormalities, seizures, and a high mortality rate. Again, during this 24 h period, cerebral calcium content showed no changes from preischemic control or from the matched saline-treated group. These data suggest that sig nificant accumulation of calcium in brain tissue is not an early event in ischemic-hyperglycemic brain damage, and thus does not provide support for a role of calcium in the production of this form of ischemic damage.