Abstract 14085: Morphine-Induced Postconditioning Modulates Mitochondrial Permeability Transition Pore Opening Via Delta-1 Opioid Receptors Activation in Isolated Rat Hearts
Introduction: It has been accepted that morphine confers cardioprotection against ischemia/reperfusion injury. Inhibition of mitochondrial permeability transition pore (MPTP) is considered as 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 hr of reperfusion. Hearts were treated with morphine with or without the OR antagonists or the MPTP opener at early reperfusion(Figure. 1). Infarct size was measured with 2,3,5-triphenyltetrazolium chloride staining.
Results: There were no significant differences in cardiodynamic variables except the decrease in heart rate in 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). Infarct limitation effect by M-Post was comparable with ischemic postconditioning (11.9 ± 2.2%, P > 0.05). Nonspecific OR antagonist naloxone (25.7 ± 1.9%, P < 0.01), δ-OR antagonist naltrindole (27.8 ± 4.3%, P < 0.05) and δ1-OR antagonist 7-benzylidenenaltrexone (24.7 ± 3.7%, P < 0.01) totally abrogated the anti-infarct effect of M-Post (Figure. 2-A). In addition, the anti-infarct effect by M-Post was also totally aborted by the MPTP opener atractyloside (26.3 ± 5.2%, P < 0.05, Figure. 2-B).
Conclusions: M-Post effectively reduces myocardial infarction. The anti-infarct effect of M-Post is mediated via activation of δ-OR, especially δ1-OR, and inhibition of MPTP opening.
- © 2010 by American Heart Association, Inc.