Vanini Giancarlo, Watson Christopher J, Lydic Ralph, Baghdoyan Helen A
Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Anesthesiology. 2008 Dec;109(6):978-88. doi: 10.1097/ALN.0b013e31818e3b1b.
Many general anesthetics are thought to produce a loss of wakefulness, in part, by enhancing gamma-aminobutyric acid (GABA) neurotransmission. However, GABAergic neurotransmission in the pontine reticular formation promotes wakefulness. This study tested the hypotheses that (1) relative to wakefulness, isoflurane decreases GABA levels in the pontine reticular formation; and (2) pontine reticular formation administration of drugs that increase or decrease GABA levels increases or decreases, respectively, isoflurane induction time.
To test hypothesis 1, cats (n = 5) received a craniotomy and permanent electrodes for recording the electroencephalogram and electromyogram. Dialysis samples were collected from the pontine reticular formation during isoflurane anesthesia and wakefulness. GABA levels were quantified using high-performance liquid chromatography. For hypothesis 2, rats (n = 10) were implanted with a guide cannula aimed for the pontine reticular formation. Each rat received microinjections of Ringer's (vehicle control), the GABA uptake inhibitor nipecotic acid, and the GABA synthesis inhibitor 3-mercaptopropionic acid. Rats were then anesthetized with isoflurane, and induction time was quantified as loss of righting reflex. Breathing rate was also measured.
Relative to wakefulness, GABA levels were significantly decreased by isoflurane. Increased power in the electroencephalogram and decreased activity in the electromyogram caused by isoflurane covaried with pontine reticular formation GABA levels. Nipecotic acid and 3-mercaptopropionic acid significantly increased and decreased, respectively, isoflurane induction time. Nipecotic acid also increased breathing rate.
Decreasing pontine reticular formation GABA levels comprises one mechanism by which isoflurane causes loss of consciousness, altered cortical excitability, muscular hypotonia, and decreased respiratory rate.
许多全身麻醉药被认为部分通过增强γ-氨基丁酸（GABA）神经传递来导致觉醒丧失。然而，脑桥网状结构中的GABA能神经传递却促进觉醒。本研究检验了以下假设：（1）与清醒状态相比，异氟烷会降低脑桥网状结构中的GABA水平；（2）向脑桥网状结构给药可增加或降低GABA水平的药物，会分别增加或减少异氟烷诱导时间。
为检验假设1，对5只猫进行开颅手术并植入永久性电极以记录脑电图和肌电图。在异氟烷麻醉和清醒状态下，从脑桥网状结构采集透析样本。使用高效液相色谱法定量GABA水平。对于假设2，将10只大鼠植入导向套管，使其对准脑桥网状结构。每只大鼠接受微量注射林格氏液（溶剂对照）、GABA摄取抑制剂尼克酸和GABA合成抑制剂3-巯基丙酸。然后用异氟烷麻醉大鼠，并将诱导时间量化为翻正反射消失。同时测量呼吸频率。
与清醒状态相比，异氟烷使GABA水平显著降低。异氟烷引起的脑电图功率增加和肌电图活动减少与脑桥网状结构GABA水平相关。尼克酸和3-巯基丙酸分别显著增加和减少异氟烷诱导时间。尼克酸还增加了呼吸频率。
降低脑桥网状结构GABA水平是异氟烷导致意识丧失、改变皮层兴奋性、肌肉张力减退和呼吸频率降低的一种机制。
