Dexmedetomidine decreases the convulsive potency of bupivacaine and levobupivacaine in rats:: Involvement of α2-adrenoceptor for controlling convulsions
Dexmedetomidine decreases the convulsive potency of bupivacaine and levobupivacaine in rats:: Involvement of α2-adrenoceptor for controlling convulsions
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DOI：
10.1213/01.ane.0000144420.87770.fe
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发表时间：
2005-03-01
影响因子：
5.7
通讯作者：
Asada, A
中科院分区：
文献类型：
--
作者：
Tanaka, K;Oda, Y;Asada, A
右美托咪定是一种高选择性α（2）-肾上腺素受体激动剂，与局麻药联合用于镇静和镇痛。我们检验了用于镇静的右美托咪定改变清醒自主呼吸大鼠中外消旋布比卡因和左布比卡因的惊厥效力的假设。在第一个实验中，雄性Sprague-Dawley大鼠随机分为6组：布比卡因组，不加右旋托咪啶组，（布比卡因对照; BC）、布比卡因与小剂量右美托咪定（BS）、布比卡因与大剂量右美托咪定（BL）、左布比卡因与无右美托咪定（BL）（左旋布比卡因对照; LC）、左布比卡因与小剂量右美托咪定（LS）和左布比卡因与大剂量右美托咪定（LL）（每组n = 10）。连续输注右美托咪定（BC组和LC组，0 μ g-kg（-1）（.）h（-1）; BS和LS组，3.6 mug-kg（-1）（.）h（-1）; BL和LL组，10.8 μ g（.）kg（-1）。h（-1））（BC和LC组，0 μ g/kg; BS和LS组，0.5 μ g/kg; BL和LL组，1.5 μ g/kg）。右美托咪啶输注开始后15分钟，开始持续输注布比卡因（BC、BS和BL组）或左布比卡因（LC、LS和LL组），输注剂量为1 mg·kg（-1）·min-1，持续输注直至发生强直性/阵挛性惊厥。右美托尼定在BC、BS、BL组和LC、LS、LL组中的镇静水平差异有统计学意义（P <0.05）。BL组和LL组布比卡因和左旋布比卡因的惊厥剂量分别显著大于BC组和LC组（P <0.01）。BL组和LL组惊厥发作时血浆和脑内布比卡因和左布比卡因浓度也高于BC组和LC组（均P <0.01）。在第二项实验中，在右美托咪定输注开始前10分钟和输注开始后5分钟给予育亨宾（1 mg/kg）完全逆转了右美托咪定的镇静作用（推注1.5 mug/kg，随后为10.8 mug-kg（-1）-h-1）。在接受育亨宾和右美托咪定的大鼠中，惊厥发作时布比卡因和左布比卡因的惊厥剂量和血浆及脑浓度显著小于仅接受右美托咪定的大鼠（所有P <0.05），并且与未接受右美托咪定或育亨宾的大鼠相似。我们得出结论，右美托咪定用于镇静降低布比卡因和左旋布比卡因在大鼠中的惊厥效力。α，β-肾上腺素能受体激动作用可能与这种抗惊厥作用有关。
Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is used in combination with local anesthetics for sedation and analgesia. We tested the hypothesis that dexmedetomidine used for sedation alters the convulsive potency of racemic bupivacaine and levobupivacaine in awake, spontaneously breathing rats. In the first experiments, male Sprague-Dawley rats were randon-dy divided into six groups: bupivacaine with no dextnedetomtidine (bupivacaine control; BC), bupivacaine with small-dose dexmedetomidine (BS), bupivacaine with large-dose dexmedetomidine (BL), levobupivacaine with no dexrnedetornidine (levobupivacaine control; LC), levobupivacaine with small-dose dexrnedetomidine (LS), and levobupivacame with large-dose dexmedetomidine (LL) (n = 10 for each group). Continuous infusion of dexmedetomidine (Groups BC and LC, 0 mug - kg(-1) (.) h(-1); Groups BS and LS, 3.6 mug - kg(-1) (.) h(-1); and Groups BL and LL, 10.8mug (.) kg(-1). h(-1)) was started after bolus injection (Groups BC and LC, 0 mug/kg; Groups BS and LS, 0.5 mug/kg; and Groups BL and LL, 1.5 mug/kg). Fifteen minutes after the start of the dexmedetomidi-ne infusion, continuous infusion of bupivacaine (Groups BC, BS, and BL) or levobupivacaine (Groups LC, LS, and LL at 1 mg - kg(-1) - min - 1 was started and continued until tonic/clonic convulsions occurred. Dexmedetornidine achieved significantly different sedation levels both in Groups BC, BS, and BL and in Groups LC, LS, and LL (P < 0.05). Convulsive doses of bupivacalne and levobupivacaine were significantly larger in Groups BL and LL than in Groups BC and LC, respectively (P < 0.01 for both). Concentrations of bupivacaine and levobupivacaine in plasma and in brain at the onset of convulsions were also larger in Groups BL and LL than in Groups BC and LC (P < 0.01 for both). In the second experiment, yohimbine (I mg/kg) administered 10 min before and 5 min after the start of dexmedetomidine infusion completely reversed the sedative effect of dexmedetomidine (bolus 1.5 mug/kg, followed by 10.8 mug - kg(-1) - h-1). Convulsive doses and plasma and brain concentrations of bupivacalne and levobupivacaine at the onset of convulsions in rats receiving yohimbine and dexmedetomidine were significantly smaller than in those receiving only dexmedeton-ddine (P < 0.05 for all) and were similar to those without dexmedetomidine or yohimbine. We conclude that dexmedetomidine used for sedation decreases the convulsive potency of both bupivacaine and levobupivacaine in rats. a,-Adrenoceptor agonism may be involved in this anticonvulsant potency.