Effect of morphine preconditioning on mitochondrial permeability transition pore after myocardial ischemia-reperfusion injury in rats.
OBJECTIVE
To investigate the effect of morphine preconditioning on mitochondrial permeability transition pore (MPTP) and its protective mechanism after myocardial ischemia-reperfusion injury.


METHODS
A rat model of ischemia-reperfusion injury was established. Forty rats were injected with 2-(3)[H] DOG and then divided into 4 groups randomly: a sham operation (S) group, an ischemia-reperfusion injury (IR) group, a morphine preconditioning (Mp+IR) group, and a cyclosporine A preconditioning (CsA+IR) group. We monitored the concentrations of serum creatine kinase-Mb (CK-Mb) and cardiac troponin I (cTnI), and measured myocardial mitochondrial 2-(3)[H] DOG, cytochrome c content, Ca(2+) concentration ([Ca(2+)]m), the velocity of Ca(2+) intake and reaction half time of mitochondrial permeability transition pore (MPTP t(1/2)) in the 4 groups.


RESULTS
The concentrations of serum CK-Mb and cTnI decreased more in the Mp+IR group and the CsA+IR group than those of the IR group. The concentrations of 2-(3)[H]DOG and [Ca(2+)]m in the IR group were evidently higher but the level of cytochrome c was lower than those of the sham operation group. The concentrations of 2-(3)[H] DOG and [Ca(2+)]m in the Mp+IR group decreased whereas the concentration of cytochrome c increased compared with those in the IR group. Mitochondrial 2-(3)[H]DOG content was positively correlated with the concentration of calcium (r=0.797, P<0.01). The 2-(3)[H]DOG and [Ca(2+)]m content were negatively correlated with cytochrome c in the IR group (r=-0.805 and r=-0.648, respectively, P<0.01). MPTP t(1/2) in the IR group was shortened evidently, and that in the Mp+IR and CsA+IR group was significantly lengthened.


CONCLUSIONS
Morphine preconditioning may have myocardial protective effect through unburdening the calcium overload and lengthening the MPTP t(1/2).
He
Zhibiao
Z
Department of Emergency, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Peng
Zaimei
Z
Jin
Liyan
L
Xu
Junmei
J
Chai
Xiangping
X
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050994:Voltage-Dependent Anion Channels / Q000187:drug effects*
D050994:Voltage-Dependent Anion Channels; D009020:Morphine; D002118:Calcium