Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea.
Anesthesiology. 2011 Feb;114(2):293-301. doi: 10.1097/ALN.0b013e3182054d22.
The goal of this in vitro study was to investigate the effects of lipid emulsion (LE) on local anesthetic levobupivacaine-induced responses in isolated rat aorta and to determine whether the effect of LE is related to the lipid solubility of local anesthetics.
Isolated rat aortic rings were suspended for isometric tension recording. The effects of LE were determined during levobupivacaine-, ropivacaine-, and mepivacaine-induced responses. Endothelial nitric oxide synthase and caveolin-1 phosphorylation was measured in human umbilical vein endothelial cells treated with levobupivacaine alone and with the addition of LE.
Levobupivacaine produced vasoconstriction at lower, and vasodilation at higher, concentrations, and both were significantly reversed by treatment with LE. Levobupivacaine and ropivacaine inhibited the high potassium chloride-mediated contraction, which was restored by LE. The magnitude of LE-mediated reversal was greater with levobupivacaine treatment than with ropivacaine, whereas this reversal was not observed in mepivacaine-induced responses. In LE-pretreated rings, low-dose levobupivacaine- and ropivacaine-induced contraction was attenuated, whereas low-dose mepivacaine-induced contraction was not significantly altered. Treatment with LE also inhibited the phosphorylation of endothelial nitric oxide synthase induced by levobupivacaine in human umbilical vein endothelial cells.
These results indicate that reversal of levobupivacaine-induced vasodilation by LE is mediated mainly through the attenuation of levobupivacaine-mediated inhibition of L-type calcium channel-dependent contraction and, in part, by inhibition of levobupivacaine-induced nitric oxide release. LE-mediated reversal of responses induced by local anesthetics may be related to their lipid solubility.
本体外研究旨在探讨脂肪乳（LE）对分离大鼠主动脉中局部麻醉药左布比卡因诱导反应的影响，并确定 LE 的作用是否与局部麻醉药的脂溶性有关。
分离的大鼠主动脉环用于等长张力记录。在左布比卡因、罗哌卡因和甲哌卡因诱导的反应中确定 LE 的作用。单独用左布比卡因和加入 LE 处理人脐静脉内皮细胞，测量内皮型一氧化氮合酶和 caveolin-1 磷酸化。
左布比卡因在较低浓度下产生血管收缩，在较高浓度下产生血管舒张，两者均被 LE 处理显著逆转。左布比卡因和罗哌卡因抑制高钾氯化物介导的收缩，而 LE 可恢复这种收缩。与罗哌卡因相比，用左布比卡因处理时，LE 介导的逆转幅度更大，而在甲哌卡因诱导的反应中未观察到这种逆转。在 LE 预处理的环中，低剂量左布比卡因和罗哌卡因诱导的收缩减弱，而低剂量甲哌卡因诱导的收缩无明显变化。LE 处理还抑制了左布比卡因在人脐静脉内皮细胞中诱导的内皮型一氧化氮合酶的磷酸化。
这些结果表明，LE 逆转左布比卡因诱导的血管舒张主要是通过减弱左布比卡因介导的 L 型钙通道依赖性收缩抑制，部分通过抑制左布比卡因诱导的一氧化氮释放来实现。LE 介导的局部麻醉药诱导反应的逆转可能与其脂溶性有关。
