The Relation between Cerebral Metabolic Rate and Ischemic Depolarization

Abstract

Background Reductions in cerebral metabolic rate may increase the brain's tolerance of ischemia. However, outcome studies suggest that reductions in cerebral metabolic rate produced by anesthetics and by hypothermia may not be equally efficacious. To examine this question, we measured the effects of hypothermia, pentobarbital, and isoflurane on the cerebral metabolic rate for glucose (CMRG) and on the time to the loss of normal membrane ion gradients (terminal ischemic depolarization) of the cortex during complete global ischemia. Methods As pericranial temperature was varied between 39 and 25 degrees C in normocapnic halothane-anesthetized rats, CMRG (using 14C-deoxyglucose) or the time to depolarization (using a glass microelectrode in the cortex) after a K(+)-induced cardiac arrest was measured. In other studies, CMRG and depolarization times were measured in normothermic animals (37.7 +/- 0.2 degrees C) anesthetized with high-dose pentobarbital or isoflurane (both producing burst suppression on the electroencephalogram) or in halothane-anesthetized animals whose temperatures were reduced to 27.4 +/- 0.3 degrees C. These three states were designed to produce equivalent CMRG values. Results As temperature was reduced from 39 to 25 degrees C, CMRG decreased from 66 to 21 microM.100 g-1.min-1 (Q10 = 2.30), and depolarization times increased from 76 to 326 s. In similarly anesthetized animals at approximately 27 degrees C, CMRG was 32 +/- 4 microM.100 g-1.min-1 (mean +/- SD), whereas in normothermic pentobarbital- and isoflurane-anesthetized rats, CMRG values were 33 +/- 3 and 37 +/- 4 microM.100 g-1.min-1, respectively (P = 0.072 by one-way analysis of variance). Despite these similar metabolic rates, the times to depolarization were markedly different: for hypothermia it was 253 +/- 29 s, for pentobarbital 109 +/- 24 s, and for isoflurane 130 +/- 28 s (P < 0.0001). Conclusions The time to terminal depolarization is believed to be a measure of the rate at which energy stores are depleted. In this study there was a strong correlation between hypothermic reductions in CMRG and increases in the time to depolarization. This finding supports the belief that metabolic suppression may offer some cerebral protection. However, equivalent reductions in CMRG produced by hypothermia and by anesthesia were not equivalent in their effects on membrane failure. Whether hypothermia slows energy depletion by some unique mechanism or directly retards depolarization is unknown.