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

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Purpose: Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. Materials and Methods: The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6×10-4 M levobupivacaine, 2×10-3 M ropivacaine, and 7×10-3 M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. Results: Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3×10-3 M)-induced vasodilation. In addition,lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. Conclusion: Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.

Abstract

Purpose: Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. Materials and Methods: The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6×10-4 M levobupivacaine, 2×10-3 M ropivacaine, and 7×10-3 M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. Results: Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3×10-3 M)-induced vasodilation. In addition,lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. Conclusion: Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.

참고문헌 (32)

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Lipid emulsion inhibits vasodilation induced by a toxic dose of bupivacaine by suppressing bupivacaine-induced PKC and CPI-17 dephosphorylation but has no effect on vasodilation induced by a toxic dose of mepivacaine권성춘, 백지석, 손주태, 옥성호, Hyunhoo Cho, Jiah Oh, Sebin Kang, Soo Hee Lee대한통증학회 · The Korean Journal of Pain2016 · 제29권 제4호Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine권성춘, 김우찬, 박경은, 박정철, 배성일, 손주태, 신일우, 옥성호, 이헌근, 정영균, 최문정대한통증학회 · The Korean Journal of Pain2014 · 제27권 제3호Lipid Emulsion in the Successful Resuscitation of Local Anesthetic Toxicity after Ankle Block곽상현, 김석재, 박상희, 유경연, 육근배, 이현정대한중환자의학회 · Acute and Critical Care2014 · 제29권 제3호베라파밀 중독의 쥐 모델에서 지방에멀젼 정맥주사의 효과강창우, 김동훈, 김태윤, 이상봉, 이수훈, 임대성, 정진희, 하대명대한임상독성학회 · 대한임상독성학회지2018 · 제16권 제1호Diazepam 전투여와 Lidocaine 투여용량이 혈중농도 및 심혈역학적 변화에 미치는 영황김세연, 김진모, 박대팔, 이경숙, 정정길영남대학교 의과대학 · Journal of Yeungnam Medical Science1993 · 제10권 제2호신경차단 시 국소마취제와 함께 사용되는 보조 약물들이덕희영남대학교 의과대학 · Journal of Yeungnam Medical Science2017 · 제34권 제2호

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