Nakashima K, Todd M M
Critical Care Medical Center, Yamaguchi University, Japan.
Anesthesiology. 1996 Jul;85(1):161-8. doi: 10.1097/00000542-199607000-00022.
Hypothermia and anesthetics may protect the brain during ischemia by blocking the release of excitatory amino acids. The effects of hypothermia (28 degrees C), pentobarbital, and isoflurane on postischemic excitatory amino acid concentrations were compared.
Rats were anesthetized with 0.8% halothane/50% N2O, vascular catheters were placed, and a glass microelectrode and microdialysis cannula were inserted into the cerebral cortex. Experimental groups were: (1) control, pericranial, t = 38 degrees C; (2) hypothermia, t = 28 degrees C; (3) pentobarbital, t = 38 degrees C; and (4) isoflurane, t = 38 degrees C. Halothane/N2O was continued in groups 1 and 2, whereas a deep burst-suppression or isoelectric electroencephalogram was achieved with the test drugs in groups 3 and 4. Cerebral metabolic rates were similar in groups 2, 3, and 4. After a baseline dialysis sample was collected, animals were killed with potassium chloride. The time to terminal depolarization was recorded, after which three consecutive 10-min dialysate samples were collected. Glutamate, aspartate, gamma-aminobutyric acid, and glycine concentrations were measured using high-performance liquid chromatography.
Times to terminal depolarization were shorter in both pentobarbital and isoflurane groups than with hypothermia (103 +/- 15 and 127 +/- 10 vs. 195 +/- 20 s respectively, mean +/- SD). However, times to terminal depolarization in all three groups were longer than in control subjects (control = 70 +/- 9s). Postdepolarization concentrations of all compounds were lower in hypothermic animals (vs. normothermic control animals), but no reductions in glutamate, aspartate, or glycine concentrations were noted in pentobarbital or isoflurane groups. gamma-Aminobutyric acid concentrations were reduced by both anesthetics, but not to the same degree as with hypothermia.
Pentobarbital and isoflurane prolonged the time to terminal depolarization, but did not influence the rate at which the extracellular concentrations of glutamate, aspartate, or glycine increased. By contrast, hypothermia reduced the release of all excitatory amino acids. These differences may explain the greater protective efficacy of hypothermia in the face of cerebral ischemia.
体温过低和麻醉剂可能通过阻断兴奋性氨基酸的释放来在缺血期间保护大脑。比较了体温过低（28摄氏度）、戊巴比妥和异氟烷对缺血后兴奋性氨基酸浓度的影响。
用0.8%氟烷/50%氧化亚氮麻醉大鼠，放置血管导管，并将玻璃微电极和微透析套管插入大脑皮层。实验组为：（1）对照组，颅周温度，t = 38摄氏度；（2）体温过低组，t = 28摄氏度；（3）戊巴比妥组，t = 38摄氏度；（4）异氟烷组，t = 38摄氏度。第1组和第2组持续使用氟烷/氧化亚氮，而第3组和第4组用受试药物使脑电图达到深度爆发抑制或等电位。第2、3和4组的脑代谢率相似。在收集基线透析样本后，用氯化钾处死动物。记录终末去极化时间，之后收集连续三个10分钟的透析液样本。使用高效液相色谱法测量谷氨酸、天冬氨酸、γ-氨基丁酸和甘氨酸的浓度。
戊巴比妥组和异氟烷组的终末去极化时间均短于体温过低组（分别为103±15秒和127±10秒，而体温过低组为195±20秒，均值±标准差）。然而，所有三组的终末去极化时间均长于对照组（对照组 = 70±9秒）。体温过低动物（与正常体温对照组动物相比）所有化合物的去极化后浓度较低，但戊巴比妥组或异氟烷组未观察到谷氨酸、天冬氨酸或甘氨酸浓度降低。两种麻醉剂均使γ-氨基丁酸浓度降低，但降低程度不如体温过低。
戊巴比妥和异氟烷延长了终末去极化时间，但不影响谷氨酸、天冬氨酸或甘氨酸细胞外浓度增加的速率。相比之下，体温过低减少了所有兴奋性氨基酸的释放。这些差异可能解释了体温过低在面对脑缺血时具有更大的保护效果。
