Zhang X, Kindel G, Wülfert E, Hanin I
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.
Acta Anaesthesiol Scand. 1998 Sep;42(8):1004-9. doi: 10.1111/j.1399-6576.1998.tb05362.x.
Mivazerol is a new and selective alpha 2-adrenergic receptor agonist devoid of hypotensive effects (1, 2). Previous studies have demonstrated that mivazerol prevents hemodynamic instability during emergence from halothane anesthesia in rats (3). The present study was to determine whether glutamate and aspartate are involved in this action of mivazerol, at the second to third thoracic segments (T2-T3) of the spinal cord.
In vivo microdialysis in combination with high-performance liquid chromatography (HPLC) was employed in the study. Blood pressure (BP) and heart rate (HR) were recorded along with intrathecal (i.t.) microdialysis perfusion.
BP, HR and i.t. release of glutamate (GLU, pmol/microliter) were stable in the rats under 1.1% halothane anesthesia. However, halothane withdrawal immediately increased BP, HR, and i.t. release of GLU, and remained elevated for at least 2 h after withdrawal of halothane. Thirty minutes prior to halothane withdrawal, intravenous (i.v.) infusion of mivazerol (15 micrograms.kg-1.h-1) almost completely prevented the increases in HR (delta 18 +/- 7 vs delta 79 +/- 7 beats/min), and in the i.t. release of GLU (delta 10.3 +/- 3.7 vs delta 30.6 +/- 5.9; 112% vs 167%). Local i.t. microinjection of mivazerol (2.5 micrograms/kg) 2 min prior to withdrawal of halothane also blocked the HR responses, as well as on the i.t. release of GLU following halothane withdrawal.
The present study demonstrates that emergence from halothane anesthesia increases i.t. release of GLU, and that mivazerol has an inhibitory effect on the above, through its direct action on the spinal cord.
米伐折罗是一种新型选择性α₂肾上腺素能受体激动剂，无降压作用（1,2）。先前的研究表明，米伐折罗可预防大鼠氟烷麻醉苏醒期间的血流动力学不稳定（3）。本研究旨在确定谷氨酸和天冬氨酸是否参与米伐折罗在脊髓胸段第二至第三节段（T2 - T3）的这一作用。
本研究采用体内微透析结合高效液相色谱（HPLC）法。记录血压（BP）、心率（HR）以及鞘内（i.t.）微透析灌注情况。
在1.1%氟烷麻醉下，大鼠的BP、HR以及i.t.谷氨酸（GLU，pmol/微升）释放量稳定。然而，停用氟烷后立即出现BP、HR升高以及i.t. GLU释放增加，且在停用氟烷后至少2小时内持续升高。在停用氟烷前30分钟，静脉输注米伐折罗（15微克·千克⁻¹·小时⁻¹）几乎完全预防了HR升高（Δ18 ± 7对比Δ79 ± 7次/分钟）以及i.t. GLU释放增加（Δ10.3 ± 3.7对比Δ30.6 ± 5.9；112%对比167%）。在停用氟烷前2分钟鞘内局部微量注射米伐折罗（2.5微克/千克）也阻断了HR反应以及停用氟烷后i.t. GLU的释放。
本研究表明，氟烷麻醉苏醒会增加i.t. GLU释放，且米伐折罗通过对脊髓的直接作用对上述情况具有抑制作用。
