title: Opioids confer myocardial tolerance to ischemia: interaction of delta opioid agonists and antagonists.
abstract: BACKGROUND
  Mammalian hibernation biology is now known to be mediated by delta opioids. The altered myocellular physiology of hibernation closely parallels that of hypothermic ischemia used to protect the heart for cardiac surgery.
  
  
  RESULTS
  The present study examined the interaction of delta opioid agonists and antagonists on myocardial tolerance to ischemia. By means of a nonhibernating isolated rabbit heart model, functional and metabolic myocardial parameters were assessed during nonischemic baseline and postischemic recovery periods. Control hearts with standard cardioplegic protection alone were compared with those with cardioplegia plus preperfusion with a delta opioid agonist, a delta opioid antagonist, or both. All hearts were then subjected to 2 hours of global ischemia. Compared with cardioplegia alone, postischemic left ventricular developed pressure, coronary flows, and myocardial oxygen consumption were all increased with administration of delta opioid agonists and decreased below baseline with delta opioid antagonists. Functional recovery of left ventricular developed pressure was improved with opioids (control hearts: 36 +/- 3 mm Hg vs hearts with cardioplegia plus delta opioid agonist: 65 +/- 5 mm Hg, P <.01) and inhibited with antagonists (control hearts: 36 +/- 3 mm Hg vs hearts with cardioplegia plus delta opioid antagonist: 17 +/- 5 mm Hg, P <.05), and true to form, the protective opioid effect was negated when combined with an antagonist (control hearts: 36 +/- 3 mm Hg vs hearts with cardioplegia plus delta opioid agonist and delta opioid antagonist: 42 +/- 4 mm Hg, P = not significant).
  
  
  CONCLUSIONS
  This study demonstrates that cardiac tolerance to ischemia may be mediated by delta opioids.
authors.affiliation: Section of Cardiac Surgery, University of Michigan, Ann Arbor, Mich, USA. sbolling@med.umich.edu
authors.forename: S F
authors.initials: SF
authors.lastname: Bolling
authors.forename: V
authors.initials: V
authors.lastname: Badhwar
authors.forename: C F
authors.initials: CF
authors.lastname: Schwartz
authors.forename: P R
authors.initials: PR
authors.lastname: Oeltgen
authors.forename: K
authors.initials: K
authors.lastname: Kilgore
authors.forename: T P
authors.initials: TP
authors.lastname: Su
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology / Q000627:therapeutic use; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology / Q000627:therapeutic use; D006324:Heart Arrest, Induced / Q000379:methods; D007036:Hypothermia, Induced / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D009929:Organ Size; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D001597:Benzylidene Compounds; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C077358:7-benzylidenenaltrexone; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-