Nakashima K, Todd M M, Warner D S
Department of Anesthesia, University of Iowa College of Medicine, Iowa City 52242-1079, USA.
Anesthesiology. 1995 May;82(5):1199-208. doi: 10.1097/00000542-199505000-00015.
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.
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.
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).
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.
脑代谢率降低可能会增加大脑对缺血的耐受性。然而，结果研究表明，麻醉剂和低温所导致的脑代谢率降低可能并非同样有效。为了研究这个问题，我们测量了低温、戊巴比妥和异氟烷对全脑缺血期间大脑葡萄糖代谢率（CMRG）以及皮质正常膜离子梯度丧失时间（终末缺血去极化）的影响。
在正常二氧化碳分压、氟烷麻醉的大鼠中，当颅周温度在39至25摄氏度之间变化时，测量K⁺诱导心脏骤停后的CMRG（使用¹⁴C - 脱氧葡萄糖）或去极化时间（使用皮质中的玻璃微电极）。在其他研究中，测量了用高剂量戊巴比妥或异氟烷麻醉的常温动物（37.7±0.2摄氏度）（两者均在脑电图上产生爆发抑制）或体温降至27.4±0.3摄氏度的氟烷麻醉动物的CMRG和去极化时间。这三种状态旨在产生相等的CMRG值。
随着温度从39摄氏度降至25摄氏度，CMRG从66降至21μmol·100g⁻¹·min⁻¹（Q₁₀ = 2.30），而去极化时间从76秒增加到326秒。在大约27摄氏度的类似麻醉动物中，CMRG为32±4μmol·100g⁻¹·min⁻¹（平均值±标准差），而在常温戊巴比妥和异氟烷麻醉的大鼠中，CMRG值分别为33±3和37±4μmol·100g⁻¹·min⁻¹（单因素方差分析，P = 0.072）。尽管代谢率相似，但去极化时间却明显不同：低温时为253±29秒，戊巴比妥时为109±24秒，异氟烷时为130±28秒（P < 0.0001）。
终末去极化时间被认为是能量储备耗尽速率的一种度量。在本研究中，CMRG的低温降低与去极化时间增加之间存在很强的相关性。这一发现支持了代谢抑制可能提供一定脑保护的观点。然而，低温和麻醉所导致的CMRG同等降低对膜功能衰竭的影响并不相同。低温是通过某种独特机制减缓能量消耗还是直接延迟去极化尚不清楚。
