Newly Published
Critical Care Medicine  |   April 2018
Free Fatty Acid Receptor G-protein–coupled Receptor 40 Mediates Lipid Emulsion-induced Cardioprotection
Author Notes
  • From the Department of Anesthesiology and Perioperative Medicine, Division of Molecular Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California.
  • The abstract from this work was presented at the Best of Basic Science Session at the American Society of Anesthesiologists 2016 Meeting, October 22 to 26, 2016, Chicago, Illinois.
    The abstract from this work was presented at the Best of Basic Science Session at the American Society of Anesthesiologists 2016 Meeting, October 22 to 26, 2016, Chicago, Illinois.×
  • Submitted for publication June 6, 2017. Accepted for publication February 19, 2018.
    Submitted for publication June 6, 2017. Accepted for publication February 19, 2018.×
  • Research Support: Supported by National Institutes of Health (Bethesda, Maryland) grant No. R01HL131182 (to Dr. Eghbali) and by a Foundation for Anesthesia Education and Research (Schaumburg, Illinois) Mentored Research Training Grant (to Dr. Umar).
    Research Support: Supported by National Institutes of Health (Bethesda, Maryland) grant No. R01HL131182 (to Dr. Eghbali) and by a Foundation for Anesthesia Education and Research (Schaumburg, Illinois) Mentored Research Training Grant (to Dr. Umar).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Eghbali: UCLA School of Medicine, BH-160CHS, Los Angeles, California 90095-7115. meghbali@ucla.edu.Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Critical Care Medicine / Cardiovascular Anesthesia / Critical Care / Pharmacology
Critical Care Medicine   |   April 2018
Free Fatty Acid Receptor G-protein–coupled Receptor 40 Mediates Lipid Emulsion-induced Cardioprotection
Anesthesiology Newly Published on April 3, 2018. doi:10.1097/ALN.0000000000002195
Anesthesiology Newly Published on April 3, 2018. doi:10.1097/ALN.0000000000002195
Abstract

Background: We have previously shown that intralipid (lipid emulsion) protects the heart against ischemia/reperfusion injury and bupivacaine-induced cardiotoxicity. However, the precise underlying mechanisms are not fully understood. Here we explored the hypothesis that free fatty acid receptor-1 or G-protein–coupled receptor 40 is expressed in the heart and that cardioprotective effects of lipid emulsion are mediated through G-protein–coupled receptor 40 in two animal models of ischemia/reperfusion injury and bupivacaine-induced cardiotoxicity.

Methods: Langendorff-perfused male mouse hearts were subjected to ischemia/reperfusion with lipid emulsion alone (1%) or with G-protein–coupled receptor 40 antagonist (GW1100, 10 µM). Additionally, cardiotoxicity was achieved in male rats with bupivacaine bolus (10 mg/kg, IV) followed by lipid emulsion alone (20%, 5 ml/kg bolus, and 0.5 ml · kg–1 · min–1 maintenance, IV) or with GW1100 pretreatment (2.5 mg/kg, IV).

Results: G-protein–coupled receptor 40 is expressed in rodent hearts. GW1100 abolished lipid emulsion-induced cardioprotection against ischemia/reperfusion in mice because rate pressure product and left ventricular developed pressure were lower than lipid emulsion alone (rate pressure product: 2,186 ± 1,783 [n = 7] vs. 11,607 ± 4,347 [n = 8]; left ventricular developed pressure: 22.6 ± 10.4 vs. 63.8 ± 20; P < 0.0001). Lipid emulsion + GW1100 also demonstrated reduced LV dP/dtmax and LV dP/dtmin (dP/dtmax = 749 ± 386 vs. 2,098 ± 792, P < 0.001; dP/dtmin = −443 ± 262 vs. −1,447 ± 546, P < 0.001).

Conclusions: G-protein–coupled receptor 40 is expressed in the rodent heart and is involved in cardioprotection mediated by lipid emulsion against ischemia/reperfusion injury and bupivacaine-induced cardiotoxicity.