Lipid Emulsion Reverses Levobupivacaine-induced Responses in Isolated Rat Aortic Vessels

• Published in: Anesthesiology (Philadelphia) 2011-02, Vol.114 (2), p.293-301
• Main Authors: OK, Seong-Ho, SOHN, Ju-Tae, LEE, Heon-Keun, CHUNG, Young-Kyun, BAIK, Ji-Seok, KIM, Jae-Gak, PARK, Sang-Seung, SUNG, Hui-Jin, SHIN, Mi-Kyung, KWON, Yong-Hyun, PARK, Chang-Shin, SHIN, Il-Woo
• Format: Article
• Language: English
• Subjects: Amides - metabolism; Amides - pharmacology; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthetics, Local - antagonists & inhibitors; Anesthetics, Local - metabolism; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Biological and medical sciences; Bupivacaine - analogs & derivatives; Bupivacaine - antagonists & inhibitors; Bupivacaine - metabolism; Caveolin 1 - drug effects; Caveolin 1 - metabolism; Cells, Cultured; Dose-Response Relationship, Drug; Emulsions; Humans; In Vitro Techniques; Lipids - pharmacology; Male; Medical sciences; Mepivacaine - metabolism; Mepivacaine - pharmacology; Nitric Oxide Synthase - drug effects; Nitric Oxide Synthase - metabolism; Rats; Rats, Sprague-Dawley; Solubility; Umbilical Veins; Vasoconstriction - drug effects; Vasodilation - drug effects
• ISSN: 0003-3022; 1528-1175
• 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.