title: Effects of Acidification and Alkalinization on the Lipid Emulsion-Mediated Reversal of Toxic Dose Levobupivacaine-Induced Vasodilation in the Isolated Rat Aorta.
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 N(ω)-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.
authors.affiliation: 1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.affiliation: 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;
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: 4. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;
authors.forename: Jongsun
authors.initials: J
authors.lastname: Yu
authors.affiliation: 4. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;
authors.forename: Youngju
authors.initials: Y
authors.lastname: Lee
authors.affiliation: 5. Department of Oral and Maxillofacial Surgery, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;
authors.forename: Mun-Jeoung
authors.initials: MJ
authors.lastname: Choi
authors.affiliation: 6. Department of Information Statistics and RINS, Gyeongsang National University, Jinju, 52828, Korea;
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Lim
authors.affiliation: 4. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;
authors.forename: Yeran
authors.initials: Y
authors.lastname: Hwang
authors.affiliation: 7. Department of Anatomy and Cell Biology and Mitochondria Hub Regulation Center, Dong-A University College of Medicine, Busan, South Korea;
authors.forename: Yeon A
authors.initials: YA
authors.lastname: Kim
authors.affiliation: 1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju-si, 52727, Republic of Korea;; 8. Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000494:pharmacology; D004655:Emulsions / Q000494:pharmacology; D006801:Humans; D000077554:Levobupivacaine; D008055:Lipids / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D004655:Emulsions; D008055:Lipids; D009569:Nitric Oxide; D000077554:Levobupivacaine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester; D002045:Bupivacaine
keywords: Aorta.; Levobupivacaine; Lipid emulsion; Nitric oxide; Pre-acidification