title: [D-Ala2,D-Leu5]-enkephalin (DADLE) and morphine-induced postconditioning by inhibition of mitochondrial permeability transition pore, in human myocardium.
abstract: The aim of the study was to examine the cardioprotective effect of morphine and Delta 2 opioid D-Ala2-Leu5 enkephalin(DADLE) administered, at early reoxygenation, in isolated human myocardium exposed to hypoxia–reoxygenation. Then,we tested the involvement of mitochondrial permeability transition pore in morphine and DADLE-induced postconditioning.Human right atrial trabeculae were obtained during cardiac surgery (coronary artery bypass and aortic valve replacement).Isometrically contracting isolated human right atrial trabeculae were exposed to 30-min hypoxia and 60-min reoxygenation(control group). In treatment groups, morphine 0.5 mmol, DADLE 10 nmol, DADLE 50 nmol and DADLE 100 nmol were administered during the first 15 min of reoxygenation. In two additional groups, morphine and DADLE 100 nmol were administered in the presence of atractyloside 50 mmol, the mitochondrial permeability transition pore opener. The force of contraction at the end of 60-min reoxygenation period (FoC60 expressed as % of baseline) was compared (mean+standard deviation) between the groups by an analysis of variance. Morphine (FoC60: 81+9% of baseline), DADLE50 nmol (FoC60: 76+11% of baseline) and DADLE 100 nmol (FoC60: 81+4% of baseline) increased significantly (P,0.001) the FoC60 as compared with the control group (FoC60: 53+3% of baseline). DADLE 10 nmol did not modify the FoC60 (50+9% of baseline; P ¼ 0.60 versus control group). The enhanced recovery of FoC60 induced by morphine and DADLE 100 nmol were abolished in the presence of atractyloside (FoC60: respectively 57+6% and 44+7% of baseline;P, 0.001). In conclusion, the administration of morphine and DADLE, in early reoxygenation period, protected human myocardium, in vitro, against hypoxia–reoxygenation injury, at least in part, by the inhibition of mitochondrial permeability transition pore opening.
authors: Department of Surgery, Chirurgia Epatopancreatica, Fondazione IRCCS San Matteo Hospital, University of Pavia.
authors: Marinella
authors: M
authors: Fuardo
authors: Sandrine
authors: S
authors: Lemoine
authors: Claudia
authors: C
authors: Lo Coco
authors: Jean Luc
authors: JL
authors: Hanouz
authors: Massimo
authors: M
authors: Massetti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000494:pharmacology; D001278:Atractyloside / Q000494:pharmacology; D003331:Coronary Vessels / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D057775:Ischemic Postconditioning / Q000379:methods*; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects* / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D009020:Morphine / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D001278:Atractyloside; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine