Correspondence  |   March 2019
Experimental Controls in Lipid Resuscitation Therapy
Author Notes
  • Massachusetts General Hospital, Boston, Massachusetts (M.R.F.). mfettiplace@partners.org
  • (Accepted for publication November 16, 2018.)
    (Accepted for publication November 16, 2018.)×
Article Information
Correspondence
Correspondence   |   March 2019
Experimental Controls in Lipid Resuscitation Therapy
Anesthesiology 3 2019, Vol.130, 516-517. doi:10.1097/ALN.0000000000002564
Anesthesiology 3 2019, Vol.130, 516-517. doi:10.1097/ALN.0000000000002564
We read with interest the recently published work by Umar et al.1  The authors assert that antagonism of free-fatty acid receptor G-protein-coupled Receptor 40 (GPR40) with a G-protein-coupled receptor small molecule inhibitor (GW1100) blocks all cardioprotective effects of lipid emulsion in animal models of ischemia-reperfusion and bupivacaine-induced cardiotoxicity. The hypothesis is appealing given that a fat-based antidote could logically work by interacting with fatty-acid receptors. We believe, however, that the study lacks appropriate controls and relies on untested assumptions to justify its conclusions.
First, the role of GPR40 in cardiac tissue is unclear. Itoh et al. identified GPR40 as a channel in the gastrointestinal-tract that modulates insulin secretion from the pancreas in response to stimulation with free-fatty acids.2  The current work is the first to identify GPR40 in cardiac tissue but fails to identify its physiologic role in normal cardiac function. Given that insulin signaling modulates bupivacaine toxicity,3–5  and that GPR40 inhibition will abolish insulin-release from the pancreas, appropriate controls for insulin and glucose levels would strengthen the argument for a cardiac (instead of pancreatic) effect. Alternatively, the authors could use a cardiac-specific knockout to confirm a cardiac specific effect.