Severe hypotension is not essential for isoflurane neuroprotection against forebrain ischemia in mice.
Severe hypotension is not essential for isoflurane neuroprotection against forebrain ischemia in mice.
复制标题
严重低血压对于异氟醚对小鼠前脑缺血的神经保护作用并不是必需的。
DOI：
10.1097/00000542-200311000-00022
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发表时间：
2003
期刊：
影响因子：
8.8
通讯作者：
Warner,DavidS
中科院分区：
文献类型：
--
作者：
Homi,HMayumi;Mixco,JavierM;Sheng,Huaxin;Grocott,HilaryP;Pearlstein,RobertD;Warner,DavidS
背景在全脑缺血的实验模型中，挥发性麻醉药提供了保护作用。到目前为止，所有被评估的模型都将深层次的全身动脉低血压作为缺血性损害的一个组成部分。方法采用异氟醚(1.2%)或芬太尼/N2O麻醉C57BL/6J小鼠，双侧颈总动脉阻断15min或20min，血压正常(平均动脉压80~110 mm Hg)或低血压(平均动脉压35 mm Hg)10min。3天后进行神经功能和组织学损伤评估。结果异氟醚可降低脑缺血10min后海马区神经元死亡百分率(双侧颈总动脉结扎+低血压：43+/-18(异氟醚组)vs 67+/-20(芬太尼/N2O组)，P=0.003；双侧颈总动脉结扎+正常血压组：49+/-27(异氟醚组)与71+/-22(芬太尼/N2O组)，P=0.003)。在所有情况下，异氟醚还可减轻CA3损伤并改善神经功能。在两种麻醉状态下，双侧颈动脉阻断加正常血压时，脑缺血内前脑血流量相似。结论无论有无全身低血压，异氟醚均能改善神经功能，减少组织学损害。这表明，异氟醚的有益作用最有可能归因于神经元水平的直接影响，而不是与深度低血压相互作用所产生的间接影响。
BackgroundVolatile anesthetics provide protection in experimental models of global cerebral ischemia. To date, all models evaluated have included profound systemic arterial hypotension as a component of the ischemic insult. This study was designed to determine if isoflurane protection persists in a global insult devoid of hypotension.MethodsC57BL/6J mice having a high incidence of posterior communicating artery atresia were anesthetized with isoflurane (1.2%) or fentanyl/N2O and subjected to bilateral carotid artery occlusion for 15 min or 20 min with normotension (80-110 mmHg mean arterial pressure) or for 10 min with hypotension (35 mmHg mean arterial pressure). Three days later, neurologic function and histologic damage were assessed. Other mice underwent measurement of intraischemic cerebral blood flow (4-iodo-N-methyl-[14C] antipyrine autoradiography) or plasma norepinephrine.ResultsIsoflurane reduced the percentage of hippocampal CA1 dead neurons (eg, 10 min bilateral carotid occlusion+ hypotension: 43+/-18 (isoflurane) vs. 67+/-20 (fentanyl/N2O), P= 0.003; 20 min bilateral carotid occlusion+ normotension: 49+/-27 (isoflurane) vs. 71+/-22 (fentanyl/N2O), P= 0.003). Isoflurane also reduced CA3 damage and improved neurologic function under all conditions. Intraischemic forebrain blood flow was similar during bilateral carotid occlusion plus normotension for the two anesthetic states. Plasma norepinephrine values were greater when hypotension was added to the ischemic insult.ConclusionsIsoflurane resulted in improved neurologic function and reduced histologic damage regardless of the presence or absence of systemic hypotension during the ischemic insult. This indicates that beneficial effects of isoflurane are most likely attributable to direct effects at the neuronal level as opposed to indirect effects resulting from interactions with profound hypotension.