Lipofundin® MCT/LCT 20% increase left ventricular systolic pressure in an<i>ex vivo</i>rat heart model via increase of intracellular calcium level

Park, Jiyoung; Kim, Yeon A; Han, Jeong Yeol; Jin, Sangkyu; Ok, Seong-Ho; Sohn, Ju-Tae; Lee, Heon Keun; Chung, Yoo Seung; Shin, Il Woo

doi:10.4097/kjae.2016.69.1.57

Cited by 12 publications

(10 citation statements)

References 24 publications

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“…In other words, considering the results of the current tension study and those of previous reports, lipid emulsion-mediated sequestration of bupivacaine, a local anesthetic with relatively high lipid solubility, appears to partly contribute to inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation [ 3 7 12 23 24 25 26 ]. In addition, lipid emulsion increases [Ca 2+ ] i [ 28 ]. As the conventional PKC α and β isoforms are calcium-dependent isoenzymes, the increased [Ca 2+ ] i induced by lipid emulsion may contribute to attenuation of bupivacaine-induced vasodilation through enhancement of PKC activation during PDBu-induced contraction [ 28 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, lipid emulsion increases [Ca 2+ ] i [ 28 ]. As the conventional PKC α and β isoforms are calcium-dependent isoenzymes, the increased [Ca 2+ ] i induced by lipid emulsion may contribute to attenuation of bupivacaine-induced vasodilation through enhancement of PKC activation during PDBu-induced contraction [ 28 29 ]. However, as lipid emulsion itself had no effect on PDBu-induced contraction ( Fig.…”

Section: Discussionmentioning

confidence: 99%

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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 mepivacaine

Cho

Kwon

et al. 2016

Korean J Pain

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BackgroundThe goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta.MethodsThe effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ([Ca2+]i) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting.ResultsLipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in [Ca2+]i. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation.ConclusionsThese results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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 mepivacaine

Cho

Kwon

et al. 2016

Korean J Pain

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“…Fettiplace et al reported that Intralipid® increased the arterial pressure of rats and enhanced the rate of intraventricular pressure increases or decreases in an isolated rat heart model 54 . Lipid emulsion (Intralipid® and Lipofundin® MCT/LCT) increased the intracellular calcium level in H9c2 rat cardiomyoblasts 55 . Moreover, Intralipid® reversed the decreased left ventricular systolic pressure resulting from levobupivacaine-induced myocardial depression of isolated rat hearts using the Langendorff preparation 56 .…”

Section: Proposed Mechanismsmentioning

confidence: 93%

Lipid Emulsion for Treating Local Anesthetic Systemic Toxicity

Ok¹,

Hong²,

Lee³

et al. 2018

Int. J. Med. Sci.

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103

133

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Lipid emulsion has been shown to be an effective treatment for systemic toxicity induced by local anesthetics, which is reflected in case reports. A systemic review and meta-analysis confirm the efficacy of this treatment. Investigators have suggested mechanisms associated with the lipid emulsion-mediated recovery of cardiovascular collapse caused by local anesthetic systemic toxicity; these mechanisms include lipid sink, a widely accepted theory in which highly soluble local anesthetics (particularly bupivacaine) are absorbed into the lipid phase of plasma from tissues (e.g., the heart) affected by local-anesthetic-induced toxicity; enhanced redistribution (lipid shuttle); fatty acid supply; reversal of mitochondrial dysfunction; inotropic effects; glycogen synthase kinase-3β phosphorylation associated with inhibition of the mitochondrial permeability transition pore opening; inhibition of nitric oxide release; and reversal of cardiac sodium channel blockade. The current review includes the following: 1) an introduction, 2) a list of the proposed mechanisms, 3) a discussion of the best lipid emulsion treatment for reversal of local anesthetic toxicity, 4) a description of the effect of epinephrine on lipid emulsion-mediated resuscitation, 5) a description of the recommended lipid emulsion treatment, and 6) a conclusion.

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“…Ca level [31]. Also, there are studies, the findings of which are opposite to those in the literature.…”

Section: Discussionmentioning

confidence: 74%

The Effects of Intravenous Lipid Emulsion Therapy in the Prevention of Depressive Effects of Propofol on Cardiovascular and Respiratory Systems: An Experimental Animal Study

Doğanay

Ak²,

Alışkan

et al. 2018

Preprint

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Background and objective: Propofol is an anesthetic agent that is frequently used in anesthesia induction, maintenance and sedation. Propofol has severe side effects such as hypotension, bradycardia and respiratory depression. Although propofol is commonly used, there is no known antidote for its toxic effects. An approach to prevent toxic effects of propofol would be beneficial. The aim of this study was to assess the effects of intravenous lipid emulsion (ILE) therapy in the prevention of depressive effects of propofol on cardiovascular and respiratory systems. Materials and methods: Twenty-eight Sprague-Dawley adult rats were randomly divided into 4 groups. The saline-administered group was determined as the Control group. The second group was administered propofol (PP group); the third group was administered ILE (ILE group), and the fourth was administered propofol with ILE therapy (ILE+PP group). Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Mean arterial blood pressure (MAP), Respiratory rate (RR), Heart rate (HR) and mortality were recorded at 10 points during 60 minutes. A repeated measures linear mixed-effect model with unstructured covariance was used to compare the groups. Results: In the PP group, SBP, DBP, MAP, RR and HR levels were declining steadily; all rats in this group died after 60 minutes. In the ILE+PP group, after a while, the decreased SBP, DBP, MAP, RR and HR levels increased SBP, DBP, MAP, RR and HR levels of the Propofol group were found to be significantly lower than those of the other groups (p<0.01). The mortality rate was 100% (surviving period, 60 min) for the PP group, whereas 0% for the ILE, ILE+PP and Control groups. Conclusion: Our results suggest that undesirable side effects that can be seen after propofol application such as hypotension, bradycardia and respiratory depression might be prevented by using ILE therapy.

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Lipofundin® MCT/LCT 20% increase left ventricular systolic pressure in anex vivorat heart model via increase of intracellular calcium level

Cited by 12 publications

References 24 publications

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 mepivacaine

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 mepivacaine

Lipid Emulsion for Treating Local Anesthetic Systemic Toxicity

The Effects of Intravenous Lipid Emulsion Therapy in the Prevention of Depressive Effects of Propofol on Cardiovascular and Respiratory Systems: An Experimental Animal Study

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