TY - JOUR
T1 - [D-Ala2,D-Leu5]-enkephalin (DADLE) and morphine-induced postconditioning by inhibition of mitochondrial permeability transition pore, in human myocardium
AU - Fuardo, Marinella
AU - Lemoine, Sandrine
AU - Lo Coco, Claudia
AU - Coco, Claudio
AU - Hanouz, Jean Luc
AU - Massetti, Massimo
PY - 2013
Y1 - 2013
N2 - 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 μmol, 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 μmol, the mitochondrial permeability transition pore opener. The force of contraction at the end of 60-min reoxygenation period (FoC(60) expressed as % of baseline) was compared (mean ± standard deviation) between the groups by an analysis of variance. Morphine (FoC(60): 81 ± 9% of baseline), DADLE 50 nmol (FoC(60): 76 ± 11% of baseline) and DADLE 100 nmol (FoC(60): 81 ± 4% of baseline) increased significantly (P < 0.001) the FoC(60) as compared with the control group (FoC(60): 53 ± 3% of baseline). DADLE 10 nmol did not modify the FoC(60) (50 ± 9% of baseline; P = 0.60 versus control group). The enhanced recovery of FoC(60) induced by morphine and DADLE 100 nmol were abolished in the presence of atractyloside (FoC(60): 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.
AB - 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 μmol, 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 μmol, the mitochondrial permeability transition pore opener. The force of contraction at the end of 60-min reoxygenation period (FoC(60) expressed as % of baseline) was compared (mean ± standard deviation) between the groups by an analysis of variance. Morphine (FoC(60): 81 ± 9% of baseline), DADLE 50 nmol (FoC(60): 76 ± 11% of baseline) and DADLE 100 nmol (FoC(60): 81 ± 4% of baseline) increased significantly (P < 0.001) the FoC(60) as compared with the control group (FoC(60): 53 ± 3% of baseline). DADLE 10 nmol did not modify the FoC(60) (50 ± 9% of baseline; P = 0.60 versus control group). The enhanced recovery of FoC(60) induced by morphine and DADLE 100 nmol were abolished in the presence of atractyloside (FoC(60): 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.
KW - DADLE
KW - morphine
KW - DADLE
KW - morphine
UR - http://hdl.handle.net/10807/41168
U2 - 10.1177/1535370212474602
DO - 10.1177/1535370212474602
M3 - Article
SN - 1535-3699
SP - N/A-N/A
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
ER -