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KMID : 0356920080540030320
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Korean Journal of Anesthesiology
2008 Volume.54 No. 3 p.320 ~ p.327
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Ischemic Postconditioning Inhibits Mitochondrial Permeability Transition Pore via Opioid Receptor Activation in Intact Rat Heart
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Lee Yong-Cheol
Jang Young-Ho
Kim Jin-Mo
Kim Ae-Ra
Lee Seung-Ryong
Kim Yoon-Nyun
Hong Ji-Hee
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Abstract
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Background :Ischemic postconditioning (Post-C), brief cycles of myocardial ischemia and reperfusion during the early phase of reperfusion, is considered as a novel adjunct strategy to protect myocardium.However, the exact mechanism remains unclear and should be determined.
Methods :The hearts of male Wistar rats were subjected to 30 min ischemia and 2 hrs reperfusion.Control rats had no intervention either before or after left coronary artery occlusion.Post-C was elicited by 6 cycles of 10s reperfusioninterspersed by 10s ischemia immediately after onset of reperfusion.Subsets of postconditioning rats were treated with drugs as followings; naloxone (non-selective opioid receptor antagonist), naltrindole (a ?-opioid receptor antagonist), SB216763 (a glycogen synthase kinase 3? inhibitor, GSK-3? inhibitor), or atractyloside (a mitochondrial permeability transition pore opener, mPTP opener).
Results :Post-C significantly reduced infarct size (15.9 ± 2.4%, P = 0.003) compared to control (29.9 ± 3.7%).The anti-infarct effect by Post-C was blocked by both naloxone (25.5 ± 3.9%, P = 0.044) and naltrindole (26.9 ± 2.3%, P = 0.022).Infarct size limiting effect by Post-C was also abolished by atractyloside (30.6 ± 3.6%, P = 0.003).In SB216763 with naloxone treated animals, the infarct size was decreased (17.4 ± 3.2%, P = 0.007) but not in SB216763 with atractyloside treated animals (27.4 ± 2.6%) compared to control.
Conclusion :These data suggest that Post-C may protect myocardium by inhibiting mPTP opening via ?-opioid receptor activation.GSK-3? is a downstream mediator of opioid receptors and an upstream mediator of mPTP opening in Post-C.(Korean J Anesthesiol 2008; 54: 320∼7)
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KEYWORD
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ischemia, mitochondria, opioid receptor, postconditioning, reperfusion
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