Int J Med Sci 2016; 13(1):68-76. doi:10.7150/ijms.13016

Research Paper

Effects of Acidification and Alkalinization on the Lipid Emulsion-Mediated Reversal of Toxic Dose Levobupivacaine-Induced Vasodilation in the Isolated Rat Aorta

Seong-Ho Ok1*, Won Ho Kim2,3*, Jongsun Yu4, Youngju Lee4, Mun-Jeoung Choi5, Dong Hoon Lim6, Yeran Hwang4, Yeon A Kim7, Ju-Tae Sohn1,8✉

1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;
2. Department of Anesthesiology and Pain Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea;
3. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Jinju-si, 52727, Republic of Korea;
4. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;
5. Department of Oral and Maxillofacial Surgery, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;
6. Department of Information Statistics and RINS, Gyeongsang National University, Jinju, 52828, Korea;
7. Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, South Korea;
8. Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
*These two authors contributed equally to this study as co-first authors.

Abstract

The goal of this in vitro study was to examine the effects of pre-acidification and pre-akalinization on the lipid emulsion-mediated reversal of toxic dose levobupivacaine-induced vasodilation in isolated rat aorta. Isolated aortic rings with and without the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) were exposed to four types of Krebs solution (pH 7.0, 7.2, 7.4, and 7.6), followed by the addition of 60 mM potassium chloride. When the toxic dose of levobupivacaine (3 × 10-4 M) produced a stable and sustained vasodilation in the isolated aortic rings that were precontracted with 60 mM potassium chloride, increasing lipid emulsion concentrations (SMOFlipid®: 0.24, 0.48, 0.95 and 1.39%) were added to generate concentration-response curves. The effects of mild pre-acidification alone and mild pre-acidification in combination with a lipid emulsion on endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells were investigated by Western blotting. Mild pre-acidification caused by the pH 7.2 Krebs solution enhanced the lipid emulsion-mediated reversal of levobupivacaine-induced vasodilation in isolated endothelium-intact aortic rings, whereas mild pre-acidification caused by the pH 7.2 Krebs solution did not significantly alter the lipid emulsion-mediated reversal of the levobupivacaine-induced vasodilation in isolated endothelium-denuded aortic rings or endothelium-intact aortic rings with L-NAME. A lipid emulsion attenuated the increased eNOS phosphorylation induced by the pH 7.2 Krebs solution. Taken together, these results suggest that mild pre-acidification enhances the lipid emulsion-mediated reversal of toxic dose levobupivacaine-induced vasodilation in the endothelium-intact aorta via the inhibition of nitric oxide.

Keywords: Lipid emulsion, Pre-acidification, Levobupivacaine, Nitric oxide, Aorta.

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How to cite this article:
Ok SH, Kim WH, Yu J, Lee Y, Choi MJ, Lim DH, Hwang Y, Kim YA, Sohn JT. Effects of Acidification and Alkalinization on the Lipid Emulsion-Mediated Reversal of Toxic Dose Levobupivacaine-Induced Vasodilation in the Isolated Rat Aorta. Int J Med Sci 2016; 13(1):68-76. doi:10.7150/ijms.13016. Available from http://www.medsci.org/v13p0068.htm