Critical Care Medicine  |   July 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. Corrected on May 9, 2018.
    Submitted for publication June 6, 2017. Accepted for publication February 19, 2018. Corrected on May 9, 2018.×
  • 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 / Basic Science / Cardiovascular Anesthesia / Critical Care / Pharmacology
Critical Care Medicine   |   July 2018
Free Fatty Acid Receptor G-protein–coupled Receptor 40 Mediates Lipid Emulsion-induced Cardioprotection
Anesthesiology 7 2018, Vol.129, 154-162. doi:10.1097/ALN.0000000000002195
Anesthesiology 7 2018, Vol.129, 154-162. 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). In bupivacaine-induced cardiotoxicity rat model, GW1100 pretreatment had no significant effect on heart rate (HR) and ejection fraction after 30 min (HR: 302 ± 17 vs. 312 ± 38; ejection fraction: 69 ± 3% vs. 73 ± 4%). GW1100 pretreatment, however, prevented lipid-rescue, with no recovery after 10 min. In the control group, lipid emulsion improved HR (215 ± 16 at 10 min) and fully rescued left ventricle function at 10 min (ejection fraction = 67 ± 8%, fractional shortening = 38 ± 6%).

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.