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

Ok, Seong-Ho; Han, Jeong Yeol; Lee, Soo Hee; Shin, Il Woo; Lee, Heon Keun; Chung, Yoo Seung; Choi, Mun Jeoung; Sohn, Ju-Tae

doi:10.4097/kjae.2013.64.4.353

Cited by 26 publications

(46 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to the recovery in ILE-treated rats, the recovery of flow in the saline group was associated with vasodilation below baseline peripheral resistance; this response was not observed in the ILE or null groups. This result agrees with other groups research, detailing the vasoconstrictive effects of ILE during recovery from local-anesthetic toxicity 25,26 .…”

Section: Discussionsupporting

confidence: 93%

Resuscitation with Lipid Emulsion

et al. 2014

View full text Add to dashboard Cite

Background Recent publications have questioned the validity of the “lipid sink” theory of lipid resuscitation while others have identified sink-independent effects and posed alternative mechanisms like hemodilution. To address these issues, we tested the dose-dependent response to intravenous lipid emulsion during reversal of bupivacaine-induced cardiovascular toxicity in vivo. Subsequently, we modeled the relative contribution of volume resuscitation, drug sequestration, inotropy and combined drug sequestration and inotropy to this response using an in silico model. Methods Rats were surgically prepared to monitor cardiovascular metrics and deliver drugs. Following catheterization and instrumentation, animals received a nonlethal dose of bupivacaine to produce transient cardiovascular toxicity, then were randomized to receive one of four treatments: 30% or 20% intravenous lipid emulsion, intravenous saline or no treatment (n = 7 per condition; 28 total animals). Recovery responses were compared to the predictions of a pharmacokinetic-pharmacodynamic model parameterized using previously published laboratory data. Results Rats treated with lipid emulsions recovered faster than did rats treated with saline or no treatment. Intravenous lipid emulsion of 30% elicited the fastest hemodynamic recovery followed in order by 20% intravenous lipid emulsion, saline, and no-treatment. An increase in arterial blood pressure underlay the recovery in both lipid-emulsion treated groups. Heart rates remained depressed in all four groups throughout the observation period. Model predictions mirrored the experimental recovery and the model that combined volume, sequestration and inotropy predicted in vivo results most accurately. Conclusion Intravenous lipid emulsion accelerates cardiovascular recovery from bupivacaine toxicity in a dose-dependent manner, driven by a cardiotonic response that complements the previously reported sequestration effect.

show abstract

Section: Discussionsupporting

confidence: 93%

Resuscitation with Lipid Emulsion

et al. 2014

View full text Add to dashboard Cite

show abstract

“…6). Taking into consideration the previous reports and current results, bupivacaine (above 1.61 × 10 -5 M)-induced relaxation appears to be associated with the inhibition of voltage-operated calcium channels [4,7,8,10]. Similar to the bupivacaine-induced relaxation observed in the current study, bupivacaine inhibits norepinephrine-induced contraction and induces vasorelaxation in isolated vessels precontracted with norepinephrine [2,3].…”

Section: Discussionsupporting

confidence: 85%

Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine

Bae

Kwon

et al. 2014

Korean J Pain

Self Cite

View full text Add to dashboard Cite

BackgroundA toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endotheliumdenuded rat aortas precontracted with phenylephrine.MethodsIsolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ([Ca2+]i) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip.ResultsPretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100 mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced [Ca2+]i decrease in the aortas precontracted with phenylephrine.ConclusionsTaken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine- induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

show abstract

“…In agreement with the lipid sink theory, which is accepted as an underlying mechanism of lipid emulsion treatment, lipid emulsions reverse toxic-dose local anesthetic-induced vasodilation in a manner that is dependent on the lipid solubility of the local anesthetic [2,3]. …”

Section: Introductionmentioning

confidence: 74%

A Lipid Emulsion Reverses Toxic-Dose Bupivacaine-Induced Vasodilation during Tyrosine Phosphorylation-Evoked Contraction in Isolated Rat Aortae

Lee

Kwon

et al. 2017

IJMS

Self Cite

View full text Add to dashboard Cite

The goal of this in vitro study was to examine the effect of a lipid emulsion on toxic-dose bupivacaine-induced vasodilation in a model of tyrosine phosphatase inhibitor sodium orthovanadate-induced contraction in endothelium-denuded rat aortae and to elucidate the associated cellular mechanism. The effect of a lipid emulsion on vasodilation induced by a toxic dose of a local anesthetic during sodium orthovanadate-induced contraction was examined. In addition, the effects of various inhibitors, either bupivacaine alone or a lipid emulsion plus bupivacaine, on protein kinase phosphorylation induced by sodium orthovanadate in rat aortic vascular smooth muscle cells was examined. A lipid emulsion reversed the vasodilation induced by bupivacaine during sodium orthovanadate-induced contraction. The lipid emulsion attenuated the bupivacaine-mediated inhibition of the sodium orthovanadate-induced phosphorylation of protein tyrosine, c-Jun NH2-terminal kinase (JNK), myosin phosphatase target subunit 1 (MYPT1), phospholipase C (PLC) γ-1 and extracellular signal-regulated kinase (ERK). These results suggest that a lipid emulsion reverses toxic-dose bupivacaine-induced vasodilation during sodium orthovanadate-induced contraction via the activation of a pathway involving either tyrosine kinase, JNK, Rho-kinase and MYPT1 or tyrosine kinase, PLC γ-1 and ERK, and this reversal is associated with the lipid solubility of the local anesthetic and the induction of calcium sensitization.

show abstract

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

Cited by 26 publications

References 31 publications

Resuscitation with Lipid Emulsion

Resuscitation with Lipid Emulsion

Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine

A Lipid Emulsion Reverses Toxic-Dose Bupivacaine-Induced Vasodilation during Tyrosine Phosphorylation-Evoked Contraction in Isolated Rat Aortae

Contact Info

Product

Resources

About