普萘洛尔提高清醒大鼠利多卡因诱发惊厥的阈值：对大脑的直接作用。
Propranolol increases the threshold for lidocaine-induced convulsions in awake rats: a direct effect on the brain.
作者信息
Nakamura Taketo, Oda Yutaka, Takahashi Ryota, Tanaka Katsuaki, Hase Ichiro, Asada Akira
机构信息
Department of Anesthesiology, Osaka City University Graduate School of Medicine, 1-5-7 Asahimachi, Abeno-ku, Osaka 545-8586, Japan.
出版信息
Anesth Analg. 2008 May;106(5):1450-5, table of contents. doi: 10.1213/ane.0b013e31816ba49d.
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 lidocaine-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 microg/kg of (S)-(-)-propranolol (propranolol) (cerebroventricle-small dose: CV-S and cerebroventricle-large dose: CV-L groups, respectively) or i.v. saline (IV-control: IV-C group), 1 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 i.v. at 4 mg x kg(-1) x 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 microg/mL, 22.5 +/- 3.5 vs 13.7 +/- 2.6 microg/mL, 82.7 +/- 7.1 vs 57.3 +/- 5.7 microg/g, P < 0.001 for all). The convulsive dose, plasma concentrations of total and protein-unbound lidocaine, 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 lidocaine-induced convulsions by directly acting on the brain.
背景
普萘洛尔是一种临床使用的β-肾上腺素能受体拮抗剂。局部麻醉药用于控制疼痛，而普萘洛尔则同时用于治疗高血压和心动过速。然而，很少有研究探讨普萘洛尔对局部麻醉药毒性的影响。我们研究了普萘洛尔对清醒、自主呼吸大鼠利多卡因诱发惊厥的影响。
方法
将雄性Sprague-Dawley大鼠随机分为六组（每组n = 8）。大鼠分别经脑室内注射生理盐水（脑室对照组：CV-C组）、10或30微克/千克的（S）-（-）-普萘洛尔（普萘洛尔）（分别为脑室小剂量组：CV-S组和脑室大剂量组：CV-L组）或静脉注射生理盐水（静脉对照组：IV-C组）、1或3毫克/千克的普萘洛尔（分别为静脉小剂量组：IV-S组和静脉大剂量组：IV-L组）进行预处理。三分钟后，以每分钟4毫克/千克的速度静脉注射利多卡因，直至出现强直阵挛性惊厥。
结果
CV-L组利多卡因的惊厥剂量显著高于CV-C组（分别为30.6±5.1和23.5±2.2毫克/千克，P = 0.008）。CV-L组利多卡因的总血浆浓度和非蛋白结合血浆浓度、惊厥发作时脑中利多卡因的浓度也显著高于CV-C组（分别为36.1±4.8和26.0±3.8微克/毫升、22.5±3.5和13.7±2.6微克/毫升、82.7±7.1和57.3±5.7微克/克，所有P均<0.001）。IV-L组利多卡因的惊厥剂量、总血浆浓度和非蛋白结合血浆浓度以及脑中利多卡因的浓度也显著高于IV-C组，且与CV-L组相当。IV-L组在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纳克/毫升）。
结论
普萘洛尔通过直接作用于脑提高了利多卡因诱发惊厥的阈值。
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