Propranolol increases the threshold for lidocaine-induced convulsions in awake rats: A direct effect on the brain
Propranolol increases the threshold for lidocaine-induced convulsions in awake rats: A direct effect on the brain
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DOI：
10.1213/ane.0b013e31816ba49d
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发表时间：
2008-05-01
影响因子：
5.7
通讯作者：
Asada, Akira
中科院分区：
文献类型：
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作者：
Nakamura, Taketo;Oda, Yutaka;Asada, Akira
背景：普萘洛尔是一种β-肾上腺素能受体拮抗剂，临床应用广泛。局部麻醉剂用于控制疼痛，而普萘洛尔同时用于治疗高血压和心动过速。然而，很少有研究普萘洛尔对局麻药毒性的影响。我们研究了普萘洛尔对利多卡因诱导的清醒自主呼吸大鼠惊厥的影响。方法：雄性SD大鼠随机分为6组（n = 8，每组）。用脑室内盐水（脑室-对照：CV-C组）、10或30 μ g/kg（S）-（-）-普萘洛尔（普萘洛尔）（分别为脑室-小剂量：CV-S和脑室-大剂量：CV-L组）或IV盐水（IV-对照：IV-C组）、1或3 mg/kg普萘洛尔（分别为IV-小剂量：IV-S和IV-大剂量：IV-L组）预处理大鼠。mg.kg结果：CV-L组的利多卡因惊厥剂量明显大于CV-C组（分别为30.6 +/- 5.1和23.5 +/- 2.2 mg/kg，P = 0.008）。CV-L组的血浆总利多卡因浓度和蛋白游离利多卡因浓度以及惊厥发作时脑中利多卡因浓度也显著高于CV-C组（36.1 +/- 4.8 vs 26.0 +/- 3.8 μ g/mL，22.5 +/- 3.5 vs 13.7 +/- 2.6 μ g/mL，82.7 +/- 7.1 vs 57.3 +/- 5.7 μ g/g，P均< 0.001）。IV-L组的惊厥剂量、总利多卡因和蛋白质未结合利多卡因的血浆浓度以及脑利多卡因浓度也显著大于IV-C组，与CV-L组相当。在IV-L组开始输注利多卡因前普萘洛尔的血浆浓度比CV-L组高约60倍（分别为554.7 +/- 104.6和9.3 +/- 6.7 ng/mL）。
BACKGROUND: Propranolol is a beta-adrenoceptor antagonist used clinically. Local anesthetics are used for controlling pain, whereas propranolol is concomitantly given to treat hypertension and tachycardia. However, there are few studies examining the effects of propranolol on the toxicity of local anesthetics. We investigated the effect of propranolol on liclocaine-induced convulsions in awake, spontaneously breathing rats.METHODS: Male Sprague-Dawley rats were randomly divided into six groups (n = 8, each group). Rats were pretreated with intracerebroventricular saline (cerebroventricle-control: CV-C group), 10 or 30 mu g/kg of (S)-(-)-propranolol (propranolol) (cerebroventricle-small dose: CV-S and cerebroventricle-large dose: CV-L groups, respectively) or IV saline (IV-control: IV-C group), I or 3 mg/kg of propranolol (IV-small dose: IV-S and IV-large dose: IV-L groups, respectively). Three minutes later, lidocaine was administered IV at 4 mg.kg(-1).min(-1) until tonic-clonic convulsions occurred.RESULTS: The convulsive dose of lidocaine in the CV-L group was significantly larger than that in the CV-C group (30.6 +/- 5.1 vs 23.5 +/- 2.2 mg/kg, respectively, P = 0.008). Plasma concentrations of total and protein-unbound lidocaine, concentrations of lidocaine in the brain at the onset of convulsions were also significantly higher in the CV-L group than those in the CV-C group (36.1 +/- 4.8 vs 26.0 +/- 3.8 mu g/mL, 22.5 +/- 3.5 vs 13.7 +/- 2.6 mu g/mL, 82.7 +/- 7.1 vs 57.3 +/- 5.7 mu g/g, P < 0.001 for all). The convulsive dose, plasma concentrations of total and protein-unbound liclocaine, and brain lidocaine in the IV-L group were also significantly larger than those in IV-C group and comparable with those in the CV-L group. The plasma concentration of propranolol before starting an infusion of lidocaine in the IV-L group was approximately 60-fold higher than that in the CV-L group (554.7 +/- 104.6 and 9.3 +/- 6.7 ng/mL, respectively).CONCLUSIONS: Propranolol increased the threshold for liclocaine-induced convulsions by directly acting on the brain.