Prostacyclin Analogue (OP-2507) Attenuates Hepatic Microcirculatory Derangement, Energy Depletion, and Lipid Peroxidation in a Rat Model of Reperfusion Injury

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 μg/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 μg/kg/min plus ischemia (1 h ischemia, 2 h reperfusion),N= 6. A laser–Doppler flowmeter andin vivomicroscopy 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 μg/kg/min reduced MDA (1.04 ± 0.27 μmol/g protein vs 2.64 ± 0.59 μmol/g protein in the ischemia and reperfusion group) and increased ATP levels (2.03 ± 0.17 μmol/g wet wt vs 0.73 ± 0.21 μmol/g wet wt in the ischemia and reperfusion group), while OP-2507 at a smaller dose (0.1 μg/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.