A COMPARISON OF THE EFFECTS OF HYPOTHERMIA, PENTOBARBITAL, AND ISOFLURANE ON CEREBRAL ENERGY STORES AT THE TIME OF ISCHEMIC DEPOLARIZATION

Background: In an accompanying article, we report that hypothermia (27 -28 degrees C) delayed postischemic cortical depolarization longer tha n did large-dose pentobarbital or isoflurane anesthesia, even though p reischemic cerebral metabolic rates for glucose were similar in the th ree groups. To examine the mechanism that may underlie these differenc es, we measured the cerebral concentrations of high-energy phosphates (including adenosine triphosphate [ATP] and adenosine diphosphate) in normal conditions and at the moment of depolarization. Methods: Rats w ere anesthetized with 0.8% halothane/50% N2O and prepared for measurem ent of the cortical direct-current potential by glass microelectrodes. Animals were assigned to one of four groups: (1) halothane/nitrous ox ide anesthesia, pericranial temperature approximately 38 degrees C; (2 ) halothane/ nitrous oxide, approximately 28 degrees C; (3) halothane/ nitrous oxide anesthesia with pentobarbital added to achieve electroen cephalographic isoelectricity, approximately 38 degrees C; or (4) 2.4% isoflurane/50% N2O anesthesia (with electroencephalographic isoelectr icity), approximately 38 degrees C. The latter three groups were chose n on the basis of earlier work showing similar cerebral metabolic rate s for glucose. In a subgroup of each, circulatory arrest was induced w ith KCl and the brain was frozen in situ (with liquid nitrogen) at the moment of cortical depolarization. In remaining animals, the brain wa s frozen without any ischemia. Tissue ATP, adenosine diphosphate, aden osine monophosphate, and phosphocreatine concentrations were measured by high-performance liquid chromatography. Results: High-energy phosph ate concentrations in nonischemic brain tissue were similar in all gro ups (e.g., ATP concentration 2.47-2.79 mu mol/g brain), With ischemia, depolarization occurred when ATP concentrations had decreased to 13-1 8% of normal. There were no significant differences in the concentrati on of any compound or in the energy charge among the groups, even thou gh the time until depolarization was much longer in hypothermic animal s (242 s) than in animals receiving large doses of anesthesia (119 and 132 s) or in normothermic halothane/nitrous oxide animals (73 s). Con clusions: The ATP/energy charge threshold for cortical depolarization was similar in all groups despite differing temperature or anesthetic conditions. Because hypothermia increased the time until depolarizatio n, the rate of decrease in ATP concentration must have been slower in these animals than in the two groups receiving large-dose anesthetics, despite similar preischemic cerebral metabolic rates for glucose. Thi s finding is similar to that of earlier studies and indicates that fac tors other than preischemic metabolic rate are responsible for control ling energy utilization after ischemia.