title: 'Opioidergic postconditioning' of heart muscle during ischemia/reperfusion injury.
abstract: BACKGROUND
  Ischemic preconditioning and postconditioning are the novel strategies of attaining cardioprotection against ischemia/reperfusion (I/R) injury. Previous studies suggested the role of opioid pathway, however the class of opioid receptors responsible for this effect in humans remains unknown. The aim of the study was to assess the influence of opioids on simulated I/R injury outcomes in the hu-man myocardium.
  
  
  METHODS
  Trabeculae of the human right atrium were electrically driven in organ bath and subjected to simulated I/R injury. Morphine (10-4M, 10-5M, 10-6M) or d-opioid receptor agonist DADLE (10-8M, 10-7M, 10-6M) was used at the time of re-oxygenation. Additional trabecula was subjected to hypoxia protocol only (Control). Contractive force of the myocardium was assessed as the maximal force of a contraction (Amax), the rate of rise of the force of a contraction (Slope L) and relaxation as the rate of decay of the force of a contraction (Slope T).
  
  
  RESULTS
  Application of morphine 10-4M resulted in increase of Amax, Slope L and Slope T during re-oxygenation period as compared to Control (77.99 ± 1.5% vs. 68.8 ± 2.2%, p < 0.05; 45.72 ± 2.9% vs. 34.12 ± 5.1%, p < 0.05; 40.95 ± 2.5% vs. 32.37 ± 4.3%, p < 0.05). Parameters were not significantly different in the lower morphine concentrations. Application of DADLE 10-6M resulted in decrease of Amax and Slope L as compared to Control (68.13 ± 5.5% vs. 76.62 ± 6.6%, p < 0.05; 28.29 ± 2.2 vs. 34.80 ± 3.9%, p < 0.05).
  
  
  CONCLUSIONS
  At re-oxygenation, morphine improves systolic and diastolic function of the human myo-cardium in the dose-dependent manner. Delta-opioid receptor stimulation attenuates systolic function of human heart muscle which remains in contrast to previous reports with animal models of I/R injury. (Cardiol J 2017; 24, 4: 419-425).
authors.affiliation: John Paul II Hospital, Department of Cardiac and Vascular Diseases, Krakow.. mkunecki@op.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kunecki
authors.forename: Wojciech
authors.initials: W
authors.lastname: Płazak
authors.forename: Tomasz
authors.initials: T
authors.lastname: Roleder
authors.forename: Jolanta
authors.initials: J
authors.lastname: Biernat
authors.forename: Tomasz
authors.initials: T
authors.lastname: Oleksy
authors.forename: Piotr
authors.initials: P
authors.lastname: Podolec
authors.forename: Krzysztof S
authors.initials: KS
authors.lastname: Gołba
mesh_terms: D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010477:Perfusion; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D002316:Cardiotonic Agents; D017465:Receptors, Opioid, delta; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine
keywords: ischemia reperfusion injury; opioids; postconditioning