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In Vitro Studies Indicate Intravenous Lipid Emulsion Acts as Lipid Sink in Verapamil Poisoning

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Abstract

Intravenous lipid emulsion (ILE), a component of parenteral nutrition, consists of a fat emulsion of soy bean oil, egg phospholipids, and glycerin. Case reports suggest that ILE may reverse hypotension caused by acute poisoning with lipophilic drugs such as verapamil, but the mechanism remains unclear. The methods used are the following: (1) measurement of ILE concentration in serum samples from a patient with verapamil poisoning treated with ILE, (2) measurement of free verapamil concentrations in human serum mixed in vitro with increasing concentrations of ILE, and (3) measurement of murine ventricular cardiomyocyte l-type Ca2+ currents, intracellular Ca2+, and contractility in response to verapamil and/or ILE. Maximum patient serum ILE concentration after infusion of 1 L ILE over 1 h was approximately 1.6 vol%. In vitro GC/MS verapamil assays showed that addition of ILE (0.03–5.0 vol%) dose-dependently decreased the free verapamil concentration in human serum. In voltage-clamped myocytes, adding ILE to Tyrode’s solution containing 5 μM verapamil recovered l-type Ca2+ currents (ICa). Recovery was concentration dependent, with significant ICa recovery at ILE concentrations as low as 0.03 vol%. ILE had no effect on ICa in the absence of verapamil. In field-stimulated intact ventricular myocytes exposed to verapamil, adding ILE (0.5 %) resulted in a rapid and nearly complete recovery of myocyte contractility and intracellular Ca2+. Our in vitro studies indicate that ILE acts as a lipid sink that rapidly reverses impaired cardiomyocyte contractility in the continued presence of verapamil.

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Acknowledgments

The work was supported in part by American Heart Association grants (post-doctoral fellowship grant to D.O.K. and established investigator grant to B.C.K.)

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Authors and Affiliations

  1. Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Medical Research Building IV, Rm. 1265, 2215B Garland Ave, Nashville, TN, 37232-0575, USA

    Dmytro O. Kryshtal, Donna Seger & Bjorn C. Knollmann

  2. Department of Pathology, Vanderbilt University, Nashville, TN, USA

    Sheila Dawling

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  1. Dmytro O. Kryshtal
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  2. Sheila Dawling
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  3. Donna Seger
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  4. Bjorn C. Knollmann
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Correspondence to Bjorn C. Knollmann.

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Kryshtal, D.O., Dawling, S., Seger, D. et al. In Vitro Studies Indicate Intravenous Lipid Emulsion Acts as Lipid Sink in Verapamil Poisoning. J. Med. Toxicol. 12, 165–171 (2016). https://doi.org/10.1007/s13181-015-0511-y

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  • DOI: https://doi.org/10.1007/s13181-015-0511-y

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