Verhaegen M, Iaizzo P A, Todd M M
Department of Anesthesia, University of Iowa College of Medicine, Iowa City 52242-1079, USA.
Anesthesiology. 1995 May;82(5):1209-15. doi: 10.1097/00000542-199505000-00016.
In an accompanying article, we report that hypothermia (27-28 degrees C) delayed postischemic cortical depolarization longer than did large-dose pentobarbital or isoflurane anesthesia, even though preischemic cerebral metabolic rates for glucose were similar in the three groups. To examine the mechanism that may underlie these differences, 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.
Rats were anesthetized with 0.8% halothane/50% N2O and prepared for measurement of the cortical direct-current potential by glass microelectrodes. Animals were assigned to one of four groups: (1) halothane/nitrous oxide 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 electroencephalographic isoelectricity, approximately 38 degrees C; or (4) 2.4% isoflurane/50% N2O anesthesia (with electroencephalographic isoelectricity), approximately 38 degrees C. The latter three groups were chosen on the basis of earlier work showing similar cerebral metabolic rates for glucose. In a subgroup of each, circulatory arrest was induced with KCl and the brain was frozen in situ (with liquid nitrogen) at the moment of cortical depolarization. In remaining animals, the brain was frozen without any ischemia. Tissue ATP, adenosine diphosphate, adenosine monophosphate, and phosphocreatine concentrations were measured by high-performance liquid chromatography.
High-energy phosphate concentrations in nonischemic brain tissue were similar in all groups (e.g., ATP concentration 2.47-2.79 mumol/g brain). With ischemia, depolarization occurred when ATP concentrations had decreased to 13-18% of normal. There were no significant differences in the concentration of any compound or in the energy charge among the groups, even though the time until depolarization was much longer in hypothermic animals (242 s) than in animals receiving large doses of anesthesia (119 and 132 s) or in normothermic halothane/nitrous oxide animals (73 s).
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 depolarization, 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. This finding is similar to that of earlier studies and indicates that factors other than preischemic metabolic rate are responsible for controlling energy utilization after ischemia.
在一篇相关文章中，我们报道了低温（27 - 28摄氏度）比大剂量戊巴比妥或异氟烷麻醉更能延长缺血后皮层去极化时间，尽管三组的缺血前脑葡萄糖代谢率相似。为了研究这些差异可能潜在的机制，我们测量了正常条件下以及去极化时刻大脑中高能磷酸盐（包括三磷酸腺苷[ATP]和二磷酸腺苷）的浓度。
用0.8%氟烷/50%氧化亚氮麻醉大鼠，并准备用玻璃微电极测量皮层直流电位。动物被分为四组之一：（1）氟烷/氧化亚氮麻醉，颅周温度约38摄氏度；（2）氟烷/氧化亚氮，约28摄氏度；（3）氟烷/氧化亚氮麻醉并添加戊巴比妥以达到脑电图等电位，约38摄氏度；或（4）2.4%异氟烷/50%氧化亚氮麻醉（脑电图等电位），约38摄氏度。后三组是根据早期显示相似脑葡萄糖代谢率的研究选择的。在每组的一个亚组中，用氯化钾诱导循环停止，并在皮层去极化时刻将大脑原位（用液氮）冷冻。在其余动物中，大脑在没有任何缺血的情况下冷冻。通过高效液相色谱法测量组织中的ATP、二磷酸腺苷、一磷酸腺苷和磷酸肌酸浓度。
所有组非缺血脑组织中的高能磷酸盐浓度相似（例如，ATP浓度为2.47 - 2.79 μmol/g脑）。缺血时，当ATP浓度降至正常的13 - 18%时发生去极化。尽管低温动物（242秒）达到去极化的时间比接受大剂量麻醉的动物（119和132秒）或正常体温的氟烷/氧化亚氮动物（73秒）长得多，但各组中任何化合物的浓度或能量电荷均无显著差异。
尽管温度或麻醉条件不同，但所有组皮层去极化的ATP/能量电荷阈值相似。由于低温增加了达到去极化的时间，尽管缺血前脑葡萄糖代谢率相似，但这些动物中ATP浓度的下降速率一定比接受大剂量麻醉的两组动物慢。这一发现与早期研究相似，表明缺血前代谢率以外的因素负责控制缺血后能量利用。
