Effect of Two Lipid Emulsions on Reversing High-Dose Levobupivacaine-Induced Reduced Vasoconstriction in the Rat Aortas

The goals of this study were to determine which lipid emulsion (Intralipid ® and Lipofundin MCT/LCT ® ) is more effective in reversing high-dose levobupivacaine-induced reduced vasoconstriction in isolated rat aortas and to examine the associated cellular mechanisms with a particular focus on the endothelium. Two lipid emulsion concentration–response curves were generated using high-dose levobupivacaine-induced reduced vasoconstriction and vasodilation of isolated aortas pretreated with or without 60 mM KCl. Endothelial nitric oxide synthase (eNOS) and caveolin-1 phosphorylation were measured in rat aortic tissue treated with levobupivacaine in the presence or absence of lipid emulsion. Dichlorofluorescein oxidation, a measure of reactive oxygen species production, was measured in lipid emulsion-treated human umbilical vein endothelial cells. In levobupivacaine (0.3 mM)-induced reduced vasoconstriction of isolated aorta, the magnitude of the Intralipid ® - and Lipofundin MCT/LCT ® -mediated reversal was not significantly different. Lipid emulsion reversal of levobupivacaine-induced reduced vasoconstriction was greater in endothelium-intact aortas than in endothelium-denuded aortas. The two lipid emulsions similarly inhibited levobupivacaine-induced eNOS phosphorylation in aortic tissue. Pretreatment with both lipid emulsions increased dichlorofluorescein oxidation. Both Intralipid ® and Lipofundin MCT/LCT ® are equally effective for vascular tone recovery from high-dose levobupivacaine-induced reduced vasoconstriction. This reversal is mediated partially by decreasing nitric oxide bioavailability.