Guyaux M, Gobert J, Noyer M, Vandevelde M, Wülfert E
UCB S.A., Pharmaceutical Sector, Chemin du Foriest, Belgium.
Acta Anaesthesiol Scand. 1998 Feb;42(2):238-45. doi: 10.1111/j.1399-6576.1998.tb05116.x.
Mivazerol (MIV) is an alpha 2-adrenoceptor agonist designed to prevent adverse cardiac outcome in perioperative patients. The present study was undertaken to determine whether the hyperdynamic state observed at emergence from halothane (HAL) anesthesia in rats could be modulated by MIV and to explore the mode of action of MIV under such conditions.
Male Sprague Dawley rats were anesthetized with 1% HAL and assisted for respiration (N2O-O2: 70-30%). MIV 2.2-15.3 micrograms.kg-1.h-1 i.v. was infused 30 min before withdrawal of anesthesia and compared for heart rate (HR) and systolic arterial blood pressure (SAP) to control animals treated with saline. In some experiments, animals were pretreated with intrathecal pertussis toxin (T2 level, 0.5 microgram, 7 d), or i.v. rauwolscine (0.34 mg/kg, 5 min) or were bilaterally stellectomized (30 min) prior to withdrawal of HAL.
Increases in HR (65 bpm, +20%) and in SAP (25 mmHg, +26%) were observed immediately upon discontinuation of HAL and remained constant for at least 30 min. The increase in HR was abolished by removal of the stellate ganglia. MIV dose-dependently inhibited the increase in HR from 4.8 micrograms.kg-1.h-1 (68% reduction, P < 0.05) without affecting HR or SAP during anesthesia. Inhibition of HR increase was of 98% at 15.3 micrograms.kg-1.h-1. This effect was abolished by rauwolscine, and partially (50%) inhibited by pertussis toxin pre-treatment.
These results demonstrate that withdrawal of HAL anesthesia in the rat produces a sustained increase in HR due to activation of the sympathetic system and that MIV inhibits this tachycardia via activation of alpha 2-adrenoceptors located at least in part in the spinal cord.
米伐折罗（MIV）是一种α2肾上腺素能受体激动剂，旨在预防围手术期患者的不良心脏结局。本研究旨在确定米伐折罗是否能调节大鼠在氟烷（HAL）麻醉苏醒时观察到的高动力状态，并探讨在此种情况下米伐折罗的作用方式。
雄性Sprague Dawley大鼠用1%氟烷麻醉并辅助呼吸（N2O - O2：70 - 30%）。在停止麻醉前30分钟静脉输注米伐折罗2.2 - 15.3微克·千克-1·小时-1，并将心率（HR）和收缩动脉血压（SAP）与用生理盐水处理的对照动物进行比较。在一些实验中，动物在停止使用氟烷前经鞘内注射百日咳毒素（T2水平，0.5微克，7天），或静脉注射育亨宾（0.34毫克/千克，5分钟），或双侧星状神经节切除（30分钟）。
停止使用氟烷后立即观察到心率（65次/分钟，增加20%）和收缩动脉血压（25毫米汞柱，增加26%）升高，并至少持续30分钟保持稳定。星状神经节切除消除了心率升高。米伐折罗剂量依赖性地抑制心率升高，从4.8微克·千克-1·小时-1时开始（降低68%，P < 0.05），且在麻醉期间不影响心率或收缩动脉血压。在15.3微克·千克-1·小时-1时心率升高抑制率达98%。育亨宾消除了这种作用，百日咳毒素预处理使其部分（50%）受到抑制。
这些结果表明，大鼠停止使用氟烷麻醉会因交感神经系统激活导致心率持续升高，且米伐折罗通过激活至少部分位于脊髓的α2肾上腺素能受体抑制这种心动过速。
