Sakai Hiroaki, Sheng Huaxin, Yates Robert B, Ishida Kazuyoshi, Pearlstein Robert D, Warner David S
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Anesthesiology. 2007 Jan;106(1):92-9; discussion 8-10. doi: 10.1097/00000542-200701000-00017.
Long-term neuroprotection by isoflurane has been questioned. The authors examined factors in experimental models potentially critical to definition of enduring isoflurane neuroprotection.
Rats were prepared for temporary middle cerebral artery occlusion (MCAO). Pericranial normothermia was maintained. Neurologic deficits (range, 0-48; 0=no deficit) and cerebral infarct volumes were measured. In experiment 1, rats underwent 50 or 80 min MCAO while awake or anesthetized with 1.8% isoflurane. Blood pressure was controlled with phenylephrine. Outcome was evaluated 2 weeks later. In experiment 2, rats underwent 50 min MCAO while awake or anesthetized with isoflurane, with outcome evaluated 8 weeks later. In experiment 3, rats underwent 50 min MCAO while awake or anesthetized with isoflurane and 2 weeks recovery. Effects of phenylephrine and the mitochondrial adenosine triphosphate-sensitive K channel antagonist 5-hydroxydecanoate were studied. In experiment 4, isoflurane-anesthetized rats underwent 50 min MCAO with permanent or temporary common carotid artery occlusion, with outcome evaluated 2 weeks later.
In experiment 1, isoflurane reduced neurologic deficit (median+/-interquartile range; awake vs. isoflurane: 11+/-12 vs. 8+/-6 for 80 min and 13+/-4 vs. 3+/-9 for 50 min; P=0.0006) and infarct size (160+/-97 vs. 84+/-62 mm for 80 min and 169+/-78 vs. 68+/-61 mm for 50 min; P<0.0001). In experiment 2, isoflurane protection persisted at 8 weeks after ischemia. In experiment 3, there was no effect of phenylephrine or 5-hydroxydecanoate. In experiment 4, permanent common carotid ligation increased infarct size threefold versus temporary occlusion.
Isoflurane repeatedly improved long-term neurologic and histologic outcome from focal ischemia independent of ischemia duration, perfusion pressure, or pretreatment with 5-hydroxydecanoate.
异氟烷的长期神经保护作用受到质疑。作者在实验模型中研究了可能对持久异氟烷神经保护作用定义至关重要的因素。
将大鼠准备用于暂时性大脑中动脉闭塞（MCAO）。维持颅周正常体温。测量神经功能缺损（范围为0 - 48；0 = 无缺损）和脑梗死体积。在实验1中，大鼠在清醒或用1.8%异氟烷麻醉状态下接受50或80分钟的MCAO。用去氧肾上腺素控制血压。2周后评估结果。在实验2中，大鼠在清醒或用异氟烷麻醉状态下接受50分钟的MCAO，8周后评估结果。在实验3中，大鼠在清醒或用异氟烷麻醉状态下接受50分钟的MCAO并恢复2周。研究了去氧肾上腺素和线粒体三磷酸腺苷敏感性钾通道拮抗剂5 - 羟基癸酸的作用。在实验4中，用异氟烷麻醉的大鼠在永久性或暂时性颈总动脉闭塞情况下接受50分钟的MCAO，2周后评估结果。
在实验1中，异氟烷减少了神经功能缺损（中位数±四分位间距；清醒与异氟烷：80分钟时为11±12对8±6，50分钟时为13±4对3±9；P = 0.0006）和梗死面积（80分钟时为160±97对84±62平方毫米，50分钟时为169±78对68±61平方毫米；P < 0.0001）。在实验2中，异氟烷的保护作用在缺血8周后持续存在。在实验3中，去氧肾上腺素或5 - 羟基癸酸无作用。在实验4中，永久性颈总动脉结扎使梗死面积比暂时性闭塞增加了两倍。
异氟烷反复改善局灶性缺血的长期神经和组织学结果，与缺血持续时间、灌注压或用5 - 羟基癸酸预处理无关。
