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  • Title: Prostacyclin analogue (OP-2507) attenuates hepatic microcirculatory derangement, energy depletion, and lipid peroxidation in a rat model of reperfusion injury.
    Author: Chen HM, Chen MF, Shyr MH.
    Journal: J Surg Res; 1998 Dec; 80(2):333-8. PubMed ID: 9878334.
    Abstract:
    BACKGROUND: Microcirculatory derangement, energy depletion, and lipid peroxidation are associated with the development of ischemia-reperfusion injury in the liver. This study investigated the effects of a prostacyclin analogue (OP-2507) on hepatic ischemia-reperfusion injury. MATERIALS AND METHODS: Adult, male Sprague-Dawley rats were divided into four treatment groups: (1) sham-operated control (laparotomy only, no ischemia), N =6; (2) ischemia control (1 h ischemia, 2 h reperfusion), N = 6; (3) intravenous infusion with OP-2507 ([15-cis-14-propylcyclohexyl]-16, 17,18,19,20-pentanor-9-deoxy-9a,6-nitrilo-PGF, methyl ether; Ono Pharmaceutical Co, Ltd, Osaka, Japan) at a dose of 1 microg/kg/min plus ischemia (1 h ischemia, 2 h reperfusion), N = 6; and (4) intravenous infusion with OP-2507 at a dose of 0.1 microg/kg/min plus ischemia (1 h ischemia, 2 h reperfusion), N = 6. A laser-Doppler flowmeter and in vivo microscopy were used to investigate hepatic microcirculation. Tissue malondialdehyde (MDA) and adenosine triphosphate (ATP) levels were determined at the end of the experiment. RESULTS: Compared with ischemia alone, OP-2507 significantly reduced the extent of microcirculatory and hemodynamic derangement following ischemia-reperfusion. The changes of mean systolic arterial pressure (MSAP) following ischemia-reperfusion showed biphasic alterations. OP-2507 at both doses significantly attenuated decreases in MSAP. OP-2507 lessened adherent leukocyte count and improved flow velocity in the sinusoids and postsinusoidal venules. OP-2507 at the dose of 1 microg/kg/min reduced MDA (1.04 +/- 0.27 micromol/g protein vs 2.64 +/- 0.59 micromol/g protein in the ischemia and reperfusion group) and increased ATP levels (2.03 +/- 0.17 micromol/g wet wt vs 0.73 +/- 0.21 micromol/g wet wt in the ischemia and reperfusion group), while OP-2507 at a smaller dose (0. 1 microg/kg/min) had lesser but significant effects on MDA and ATP alterations. CONCLUSION: This study demonstrates that OP-2507 treatment of ischemia can ameliorate ischemia-reperfusion injury of the rat liver.
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