The Relation between Cerebral Metabolic Rate and Ischemic Depolarization: A Comparison of the Effects of Hypothermia, Pentobarbital, and Isoflurane

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 Celsius in normocapnic halothane-anesthetized rats, CMRG (using14 Carbon-deoxyglucose) or the time to depolarization (using a glass microelectrode in the cortex) after a Potassium sup + -induced cardiac arrest was measured. In other studies, CMRG and depolarization times were measured in normothermic animals (37.7 plus/minus 0.2 degree Celsius) 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 plus/minus 0.3 degree Celsius. These three states were designed to produce equivalent CMRG values.

Results: As temperature was reduced from 39 to 25 degrees Celsius, CMRG decreased from 66 to 21 micro Meter *symbol* 100 g sup -1 *symbol* min1 (Q10 = 2.30), and depolarization times increased from 76 to 326 s. In similarly anesthetized animals at approximately 27 degrees Celsius, CMRG was 32 plus/minus 4 micro Meter *symbol* 100 g sup -1 *symbol* min sup -1 (mean plus/minus SD), whereas in normothermic pentobarbital- and isoflurane-anesthetized rats, CMRG values were 33 plus/minus 3 and 37 plus/minus 4 micro Meter *symbol* 100 g1 *symbol* min sup -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 plus/minus 29 s, for pentobarbital 109 plus/minus 24 s, and for isoflurane 130 plus/minus 28 s (P < 0.0001).