Ischemic Postconditioning Inhibits Mitochondrial Permeability Transition Pore via Opioid Receptor Activation in Intact Rat Heart.

Lee,  Yong Cheol; Jang,  Young Ho; Kim,  Jin Mo; Kim,  Ae Ra; Lee,  Seung Ryong; Kim,  Yoon Nyun; Hong,  Ji Hee

doi:2008.54.3.320

Korean J Anesthesiol > Volume 54(3); 2008 > Article

Original Article

Korean Journal of Anesthesiology 2008;54(3):320-327.
DOI: https://doi.org/10.4097/kjae.2008.54.3.320

Ischemic Postconditioning Inhibits Mitochondrial Permeability Transition Pore via Opioid Receptor Activation in Intact Rat Heart.

Yong Cheol Lee, Young Ho Jang, Jin Mo Kim, Ae Ra Kim, Seung Ryong Lee, Yoon Nyun Kim, Ji Hee Hong

¹Department of Anesthesiology and Pain Medicine, School of Medicine, Keimyung University, Daegu, Korea. eonjo@hotmail.com
²Department of Pharmacology, School of Medicine, Keimyung University, Daegu, Korea.

Abstract

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 delta-opioid receptor antagonist), SB216763 (a glycogen synthase kinase 3beta inhibitor, GSK-3beta 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.
CONCLUSIONS
These data suggest that Post-C may protect myocardium by inhibiting mPTP opening via delta-opioid receptor activation.GSK-3beta is a downstream mediator of opioid receptors and an upstream mediator of mPTP opening in Post-C.

Key Words: ischemia; mitochondria; opioid receptor; postconditioning; reperfusion