Clinical toxicology : the official journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists
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Theories regarding the mechanism of intravenous fat emulsion for bupivacaine cardiotoxicity include creation of an intravascular lipid sink into which the cardiotoxic drug is sequestered, an improvement of impaired cardiac metabolism, and restoration of cardiomyocyte function by increasing intracellular calcium. However, work in this area is inconclusive and a more mechanistic explanation is desirable. We used a heterologous expression system (HEK-293 cells) and voltage clamp techniques to study the electrophysiologic effects of bupivacaine, polyunsaturated, and saturated fatty acids on sodium current (I(Na)) in stable cell lines expressing human cardiac sodium channels. ⋯ Simultaneous exposure to bupivacaine and fatty acids reduced both the tonic and use dependent block compared with bupivacaine alone. Reduction of bupivacaine-induced I(Na) block was greatest in cells treated with linolenic acid. These results suggest that the salutary effects of intravenous fat emulsion may be, in part, due to a direct modulatory effect of fatty acids on cardiac sodium channels.