Vasodilation increases the threshold for bupivacaine-induced convulsions in rats
Vasodilation increases the threshold for bupivacaine-induced convulsions in rats
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DOI：
10.1213/01.ane.0000101984.50597.e9
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发表时间：
2004-03-01
影响因子：
5.7
通讯作者：
Asada, A
中科院分区：
文献类型：
--
作者：
Oda, Y;Funao, T;Asada, A
布比卡因通过外周和中枢神经系统（CNS）机制影响血管阻力。由于血管收缩剂增加IV布比卡因的CNS毒性，血管扩张剂可降低其CNS毒性。我们检验了血管扩张剂降低清醒、自主呼吸大鼠布比卡因中枢神经系统毒性的假设。雄性SD大鼠随机分为对照组（C）、尼卡地平组（N）和酚妥拉明组（P），每组12只。以1 mg/kg/min的速率IV给予外消旋布比卡因，直至发生强直/阵挛性惊厥。C组、N组和P组分别用生理盐水、尼卡地平（0.4 μ g/min）和酚妥拉明（5 min内10 μ g/min，此后50 μ g/min）与布比卡因同时给药。C组输注布比卡因后平均动脉血压显著升高，N组和P组在惊厥发作前维持在基线水平。C组布比卡因的惊厥剂量为5.8 ± 1.5 mg/kg，但N组和P组显著更高（分别为7.6 ± 1.5和8.1 ± 1.1 mg/kg，P = 0.02和0.001）。然而，三组间惊厥发作时布比卡因的总血浆浓度或蛋白质未结合血浆浓度或脑中布比卡因浓度无差异。我们的结论是尼卡地平和酚妥拉明增加累积剂量，但不影响布比卡因诱导惊厥所需的阈值血浆或脑浓度。
Bupivacaine affects the vascular resistance by peripheral and central nervous system (CNS) mechanisms. As vasoconstrictors increase the CNS toxicity of IV bupivacaine, vasodilators may decrease its CNS toxicity. We examined the hypothesis that vasodilators decrease the CNS toxicity of bupivacaine in awake, spontaneously breathing rats. Male Sprague-Dawley rats were randomly divided into control (C), nicardipine (N), and phentolamine (P) groups (n = 12 in each group). Racemic bupivacaine was administered IV at 1 mg/kg/min until tonic/clonic convulsions occurred. Saline, nicardipine (0.4 mug/min), and phentolamine (10 mug/min within 5 min, 50 mug/min thereafter) were simultaneously administered with bupivacaine in groups C, N, and P, respectively. Mean arterial blood pressure was significantly increased by infusion of bupivacame in group C and was maintained at baseline levels before the onset of convulsions in groups N and P. The convulsive dose of bupivacaine in group C was 5.8 +/- 1.5 mg/kg, but was significantly larger in groups N and P (7.6 +/- 1.5 and 8.1 +/- 1.1 mg/kg, P = 0.02 and 0.001, respectively). However, there were no differences in total or protein-unbound plasma concentration of bupivacaine or in concentration of bupivacaine in the brain at the onset of convulsions among the 3 groups. We conclude that nicardipine and phentolamine increase the cumulative dose but do not affect the threshold plasma or brain concentrations required for bupivacaine-induced convulsions.