Korean J Anesthesiol.  2008 Mar;54(3):320-327. 10.4097/kjae.2008.54.3.320.

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

• Lee YC
• Jang YH
• Kim JM
• Kim AR
• Lee SR
• Kim YN
• Hong JH

• KMID: 2239820
• DOI: http://doi.org/10.4097/kjae.2008.54.3.320

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.

Keyword

ischemia; mitochondria; opioid receptor; postconditioning; reperfusion

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Atractyloside
Coronary Vessels
Glycogen Synthase Kinase 3
Glycogen Synthase Kinases
Heart
Humans
Indoles
Ischemia
Ischemic Postconditioning
Male
Maleimides
Mitochondria
Mitochondrial Membrane Transport Proteins
Myocardial Ischemia
Myocardium
Naloxone
Naltrexone
Permeability
Rats
Rats, Wistar
Receptors, Opioid
Reperfusion
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Atractyloside
Glycogen Synthase Kinase 3
Glycogen Synthase Kinases
Indoles
Maleimides
Mitochondrial Membrane Transport Proteins
Naloxone
Naltrexone
Receptors, Opioid