Wu Gangming, Sun Bin, Liu L I, Zhou Jun, Mo Liqun, Ren Changhe, Ou Cehua
Department of Anesthesiology and Pain, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China.
Exp Ther Med. 2015 Sep;10(3):1133-1138. doi: 10.3892/etm.2015.2594. Epub 2015 Jun 24.
The aim of the present study was to investigate the effect of intravenously administered lipid emulsion on local anesthetic (LA)-induced central nervous system (CNS) toxicity. A total of 100 male Sprague Dawley rats were allocated at random into the following groups: Sham (A), lidocaine (B), levobupivacaine (C) and ropivacaine (D). Groups B-D were each subdivided into three subgroups: Toxic, post-conditioning and pre-conditioning. Intracerebroventricular injections of 0.9% normal saline (sham group) or LA were administered via microsyringe; in addition, a 20% lipid emulsion was injected into tail vein prior to the LA injection (pre-conditioning subgroups) or following rat respiratory arrest (post-conditioning subgroups). The heart rate, blood pressure, neurological behavior scores, neuronal density and time from LA injection to respiratory arrest, apnea and start of arrhythmia were measured. Rats in the toxic groups died due to respiratory arrest following the injection of LA into the lateral ventricle. Rats in the post-conditioning subgroups were resuscitated from the LA-induced respiratory arrest, while the pre-conditioning subgroup rats exhibited no respiratory arrest. No significant differences in heart rate were observed between the toxic and post-conditioning subgroups in the levobupivacaine and ropivacaine groups (P>0.05); however, a significant difference was observed between these treatment groups and the rats treated with lidocaine (P<0.01). A significant difference was also observed in the time from the LA injection to the onset of arrhythmia among the rats in groups B, C and D (P<0.01). No significant differences in the neurological behavior scores and neuronal density were observed in the hippocampal CA1 zone among group C and D rats in the post- and pre-conditioning subgroups at various time-points following treatment. Beyond that, the same phenomena regarding neurological behavior scores was observed in post- and pre-conditioning subgroups of group B at 12 and 24 h treatment, contrasting with the statistically significant difference between post- and pre-conditioning subgroups at 6 h treatment (P<0.01). The results of the present study therefore indicate that pre- and post-conditioning with lipid emulsion effectively mitigates LA-induced CNS toxicity in rats.
本研究的目的是探讨静脉注射脂质乳剂对局部麻醉药(LA)诱导的中枢神经系统(CNS)毒性的影响。总共100只雄性Sprague Dawley大鼠被随机分配到以下组:假手术组(A)、利多卡因组(B)、左旋布比卡因组(C)和罗哌卡因组(D)。B - D组再各自分为三个亚组:中毒组、后处理组和预处理组。通过微量注射器经脑室内注射0.9%生理盐水(假手术组)或LA;此外,在LA注射前(预处理亚组)或大鼠呼吸骤停后(后处理亚组)经尾静脉注射20%脂质乳剂。测量心率、血压、神经行为评分、神经元密度以及从LA注射到呼吸骤停、呼吸暂停和心律失常开始的时间。中毒组大鼠在向侧脑室注射LA后因呼吸骤停死亡。后处理亚组的大鼠从LA诱导的呼吸骤停中复苏,而预处理亚组的大鼠未出现呼吸骤停。左旋布比卡因和罗哌卡因组的中毒亚组和后处理亚组之间心率无显著差异(P>0.05);然而,这些治疗组与利多卡因治疗的大鼠之间存在显著差异(P<0.01)。B、C和D组大鼠从LA注射到心律失常发作的时间也存在显著差异(P<0.01)。在治疗后不同时间点,C组和D组大鼠后处理亚组和预处理亚组海马CA1区的神经行为评分和神经元密度无显著差异。除此之外,B组后处理亚组和预处理亚组在治疗12小时和24小时时神经行为评分出现相同现象,与治疗6小时时后处理亚组和预处理亚组之间的统计学显著差异形成对比(P<0.01)。因此,本研究结果表明脂质乳剂预处理和后处理可有效减轻大鼠LA诱导的CNS毒性。