Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility

Abstract

Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency) of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine) were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED50) of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED50) of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED50 in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r2 = 0.9563; P < 0.001). The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa.

Lipid emulsion-mediated reversal of toxic-dose aminoamide local anesthetic-induced vasodilation in isolated rat aorta

“…The n-octanol/buffer partition coefficients were 346 (bupivacaine), 115 (ropivacaine), 43 (lidocaine), and 21 (mepivacaine) [22]. Together with the findings of previous reports, our study shows that the magnitude of lipid emulsion-mediated reversal correlates with the lipid solubility of the local anesthetic [12,22]. One of underlying mechanisms of lipid emulsion-induced reversal of local anesthetic systemic toxicity is the "lipid sink" theory, which postulates that the lipid emulsion extracts local anesthetics from tissues into the lipid phase [23].…”

“…Intralipid®, which consists of 100% long-chain triglycerides, is commonly used to treat local anesthetic systemic toxicity, and Lipofundin® MCT/LCT, which consists of 50% long-chain triglycerides and 50% medium-chain triglycerides, is sometimes used to treat local anesthetic systemic toxicity [1-8]. Vaconstriction potency induced by local anesthetics is mainly determined by lipid solubility, among the physicochemical properties of local anesthetics [12]. However, studies investigating the ability of these two lipid emulsions (Lipofundin® MCT/LCT and Intralipid®) to extract local anesthetics and promote recovery from cardiac arrest induced by a toxic dose of bupivacaine have reported inconsistent results [16-19].…”

Lipid Emulsions Enhance the Norepinephrine-Mediated Reversal of Local Anesthetic-Induced Vasodilation at Toxic Doses

“…Local anesthetic (levobupivacaine, ropivacaine, and mepivacaine) treatment of isolated endothelium-denuded rat aorta produces vasoconstriction at low doses and vasodilation at high doses 7,17. Lipid emulsion also reverses high-dose local anesthetic-induced vasodilation in a manner dependent on the lipid solubility of local anesthetics 7.…”

“…Lipid emulsion also reverses high-dose local anesthetic-induced vasodilation in a manner dependent on the lipid solubility of local anesthetics 7. Thus, based on previous studies and lipid emulsion concentrations, which did not significantly affect high-dose local anesthetic-induced vasodilation in the preliminary experiment, both high-dose local anesthetic concentrations to produce vasodilation and lipid emulsion concentrations were chosen in our in vitro experiment 7,17. After administering high doses of local anesthetics [6×10 -4 M levobupivacaine (levobupivacaine group), 2×10 -3 M ropivacaine (ropivacaine group), and 7×10 -3 M mepivacaine (mepivacaine group)] to produce stable and sustained vasodilation in endothelium-denuded aorta precontracted with isotonic 60 mM KCl, high-dose local anesthetic-induced vasodilated aortas were treated with or without lipid emulsions (0.30, 0.49, 1.40, and 2.16%) for 5 min before the addition of norepinephrine.…”

0.5% levobupivacaine versus 0.5% ropivacaine: Are they different in ultrasound-guided sciatic block?

“…[ 15 16 ] It was recently demonstrated that Levo is more lipophilic and is a more potent vasoconstrictor than Ropi. [ 23 ] We conjecture that these two properties can lead to greater delay in vascular absorption of 0.5% Levo versus its comparator.…”