title: Involvement of Opioid Receptors in the Lipid Rescue of Bupivacaine-Induced Cardiotoxicity.
abstract: BACKGROUND
  Lipid emulsion (LE) has been successfully used for resuscitation of local anesthetic cardiotoxicity caused by bupivacaine overdose. Opioid receptors have been shown to play a key role in cardio protection. We explored whether this rescue action of LE is mediated through opioid receptors.
  
  
  METHODS
  Asystole was induced by bupivacaine (10 mg/kg over 20 seconds, IV) in young male Sprague-Dawley rats, and resuscitation with LE (intralipid 20%; 5 mL/kg bolus and 0.5 mL/kg/min maintenance) was started immediately. The rats were pretreated 2 minutes before inducing asystole with nonselective opioid receptor antagonists such as naloxone and naloxone methiodide, as well as highly selective opioid receptor antagonists for subtype κ, δ, and µ or phosphate buffer solution as a control. Heart rates and ejection fractions were measured using echocardiography.
  
  
  RESULTS
  LE rescue of bupivacaine cardiotoxicity was prevented by high-dose (1 mg/kg) naloxone but not by lower doses of naloxone (1, 5, and 10 µg/kg), by naloxone methiodide (which does not cross the blood-brain barrier), and by a selective δ- and κ-opioid receptor antagonists at a higher (10 mg/kg) dose. Successful LE rescue was not affected by highly selective µ-opioid receptor antagonists. δ-Opioid receptor antagonist (10 mg/kg) pretreatment also resulted in reduced phosphorylation level of cardiac glycogen synthase kinase-3β in rats that were not resuscitated by LE compared with control.
  
  
  CONCLUSIONS
  Our data highlight the involvement of peripheral δ- and κ-opioid receptors in the rescue action of LE.
authors.affiliation: From the Department of Anesthesiology, University of California Los Angeles, Los Angeles, California.
authors.forename: Parisa
authors.initials: P
authors.lastname: Partownavid
authors.forename: Salil
authors.initials: S
authors.lastname: Sharma
authors.forename: Jignyuan
authors.initials: J
authors.lastname: Li
authors.forename: Soban
authors.initials: S
authors.lastname: Umar
authors.forename: Siamak
authors.initials: S
authors.lastname: Rahman
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Eghbali
mesh_terms: D000779:Anesthetics, Local; D000818:Animals; D002045:Bupivacaine; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006323:Heart Arrest / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009292:Narcotic Antagonists / Q000494:pharmacology; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D002045:Bupivacaine