The Effects of Lipid Infusion on Myocardial Function and Bioenergetics in l-Bupivacaine Toxicity in the Isolated Rat Heart

Stehr, Sebastian; Ziegeler, J; Pexa, Annette; Oertel, Reinhard; Deußen, Andreas; Koch, Thea; Hübler, Matthias

doi:10.1213/01.ane.0000248220.01320.58

Cited by 144 publications

(92 citation statements)

References 27 publications

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“…Although more and more animal studies have shown a positive effect of lipid infusion in local anaestheticinduced toxicity [1][2][3][4], Professor Wildsmith is of course correct in considering neither our case, nor the case of lipid infusion reported by Rosenblatt [5], to provide definite proof of human lipid effects. For this, more human cases have to be documented and compared.…”

Section: A Replymentioning

confidence: 74%

Local anaesthetic toxicity: prevention or cure?

Wildsmith¹

2006

Anaesthesia

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Section: A Replymentioning

confidence: 74%

Local anaesthetic toxicity: prevention or cure?

Wildsmith¹

2006

Anaesthesia

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“…The tendency for bupivacaine to preferentially move into the lipid phase of plasma in the presence of ILE has been demonstrated in both in vivo and in vitro models, lending support to this theory [4,19]. A second speculated mechanism is that ILE may increase myocardial calcium levels leading to improved contractility [20,21]. A third possibility is that ILE may improve myocardial ATP synthesis by increasing the amount of available fatty acid substrate [22,23].…”

Section: Discussionmentioning

confidence: 90%

Intravenous Lipid Emulsion Alters the Hemodynamic Response to Epinephrine in a Rat Model

et al. 2013

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Intravenous lipid emulsion (ILE) is an adjunctive antidote used in selected critically ill poisoned patients. These patients may also require administration of advanced cardiac life support (ACLS) drugs. Limited data is available to describe interactions of ILE with standard ACLS drugs, specifically epinephrine. Twenty rats with intra-arterial and intravenous access were sedated with isoflurane and split into ILE or normal saline (NS) pretreatment groups. All received epinephrine 15 μm/kg intravenously (IV). Continuous mean arterial pressure (MAP) and heart rate (HR) were monitored until both indices returned to baseline. Standardized t tests were used to compare peak MAP, time to peak MAP, maximum change in HR, time to maximum change in HR, and time to return to baseline MAP/HR. There was a significant difference (p=0.023) in time to peak MAP in the ILE group (54 s, 95 % CI 44-64) versus the NS group (40 s, 95 % CI 32-48) and a significant difference (p=0.004) in time to return to baseline MAP in ILE group (171 s, 95 % CI 148-194) versus NS group (130 s, 95 % CI 113-147). There were no significant differences in the peak change in MAP, peak change in HR, time to minimum HR, or time to return to baseline HR between groups. ILE-pretreated rats had a significant difference in MAP response to epinephrine; ILE delayed the peak effect and prolonged the duration of effect of epinephrine on MAP, but did not alter the peak increase in MAP or the HR response.

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“…2 In an isolated rat heart model perfused with L-bupivacaine solution, Stehr et al observed a rapid increase in myocardial contractility and left ventricular systolic pressure after administration of a lipid emulsion. 3 They attributed this response primarily to a direct inotropic effect, even though a local anesthetic plasma-binding effect of lipids could not be excluded. Direct activation of the Ca V by fatty acids could at last partly explain the early effects of lipid emulsions on myocardial toxicity of local anesthetics, as has been proposed for calcium channel blocking agents.…”

Section: To the Editormentioning

confidence: 99%

Hemodynamic effects of lipid emulsion after local anesthetic intoxication may be due to a direct effect of fatty acids on myocardial voltage-dependent calcium channels

Pennec¹,

Guillouët²,

Rannou³

et al. 2010

Can J Anesth/J Can Anesth

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We read with great interest the review article by Dillane et al. on local anesthetic systemic toxicity. 1 The authors considered two hypotheses regarding the mechanism of action of lipid emulsions. The first hypothesis was pharmacological, wherein a circulating lipid sink extracts lipophilic local anesthetic from either plasma or tissues. The second hypothesis was metabolic, invoking reversion of the local anesthetic inhibition of the myocardial fatty acid oxidation. We suggest that a third mechanism could be involved, i.e., a direct stimulation of the voltage-gated calcium channels (Ca V ) of cardiomyocytes by long-chain fatty acids. 2 Huang et al. showed that long-chain fatty acids could activate myocardial Ca V directly and then induce a dose-dependent increase of calcium current. IntralipidÒ solution contains mainly oleic and linoleic acids (23.5% and 53%, respectively, according to laboratory data) that induce a strong and early increase (within two minutes) of the calcium current in the cardiomyocytes. 2 In an isolated rat heart model perfused with L-bupivacaine solution, Stehr et al. observed a rapid increase in myocardial contractility and left ventricular systolic pressure after administration of a lipid emulsion. 3 They attributed this response primarily to a direct inotropic effect, even though a local anesthetic plasma-binding effect of lipids could not be excluded. Direct activation of the Ca V by fatty acids could at last partly explain the early effects of lipid emulsions on myocardial toxicity of local anesthetics, as has been proposed for calcium channel blocking agents. 4,5

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The Effects of Lipid Infusion on Myocardial Function and Bioenergetics in l-Bupivacaine Toxicity in the Isolated Rat Heart

Abstract: Lipid application in l-bupivacaine-induced cardiac depression had a significant positive inotropic effect, which we would attribute to a direct inotropic effect. However, in an isolated heart model, indirect, local anesthetic plasma-binding effect of lipids cannot be excluded.

Cited by 144 publications

References 27 publications

Local anaesthetic toxicity: prevention or cure?

Local anaesthetic toxicity: prevention or cure?

Intravenous Lipid Emulsion Alters the Hemodynamic Response to Epinephrine in a Rat Model

Hemodynamic effects of lipid emulsion after local anesthetic intoxication may be due to a direct effect of fatty acids on myocardial voltage-dependent calcium channels

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