Korean J Anesthesiol.  2011 Jul;61(1):69-74. 10.4097/kjae.2011.61.1.69.

Morphine-induced postconditioning modulates mitochondrial permeability transition pore opening via delta-1 opioid receptors activation in isolated rat hearts

• Kim JH
• Chun KJ
• Park YH
• Kim J
• Kim JS
• Jang YH
• Lee MY
• Park JH

• KMID: 2092306
• DOI: http://doi.org/10.4097/kjae.2011.61.1.69

Abstract

BACKGROUND
It is generally accepted that morphine affords cardioprotection against ischemia/reperfusion injury. Inhibition of the mitochondrial permeability transition pore (MPTP) is considered an end target for cardioprotection. The aim of this study was to investigate the involvement of opioid receptors (OR) and MPTP in morphine-induced postconditioning (M-Post).
METHODS
Isolated rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Hearts were treated with 1 microM morphine, with or without the OR antagonists or a MPTP opener at early reperfusion. Infarct size was measured with 2,3,5-triphenyltetrazolium chloride staining.
RESULTS
There were no significant differences in cardiodynamic variables except a decrease in heart rate in the M-Post group (P < 0.01 vs. control) after reperfusion. M-Post dramatically reduced infarct-risk volume ratio (9.8 +/- 2.5%, P < 0.001 vs. 30.0 +/- 3.7% in control). This beneficial effect on infarct volume by M-Post was comparable with ischemic postconditioning (11.9 +/- 2.2%, P > 0.05). The nonspecific OR antagonist naloxone (25.7 +/- 1.9%, P < 0.01), the delta-OR antagonist naltrindole (27.8 +/- 4.3%, P < 0.05) and delta1-OR antagonist 7-benzylidenenaltrexone (24.7 +/- 3.7%, P < 0.01) totally abrogated the anti-infarct effect of M-Post. In addition, the anti-infarct effect by M-Post was also totally blocked by the MPTP opener atractyloside (26.3 +/- 5.2%, P < 0.05).
CONCLUSIONS
M-Post effectively reduces myocardial infarction. The anti-infarct effect by M-Post is mediated via activation of delta-OR, especially delta1-OR, and inhibition of the MPTP opening.

Keyword

Mitochondrial permeability transition pore; Morphine; Opioid receptors; Postconditioning; Reperfusion injury

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Atractyloside
Benzylidene Compounds
Heart
Heart Rate
Ischemia
Ischemic Postconditioning
Mitochondrial Membrane Transport Proteins
Morphine
Myocardial Infarction
Naloxone
Naltrexone
Permeability
Rats
Receptors, Opioid
Reperfusion
Reperfusion Injury
Tetrazolium Salts
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Atractyloside
Benzylidene Compounds
Mitochondrial Membrane Transport Proteins
Morphine
Naloxone
Naltrexone
Receptors, Opioid
Tetrazolium Salts