Prostacyclin analogue (OP-2507) attenuates hepatic microcirculatory derangement, energy depletion, and lipid peroxidation in a rat model of reperfusion injury

Background Microcirculatory derangement, energy depletion, and lipid peroxi dation are associated with the development of ischemia-reperfusion injury i n the liver. This study investigated the effects of a prostacyclin analogue (OP-2507) on hepatic ischemia-reperfusion injury. Materials and Methods. A dult, male Sprague-Dawley rats were divided into four treatment groups: (1) sham-operated control (laparotomy only, no ischemia), N =6; (2) ischemia c ontrol (1 h ischemia, 2 h reperfusion), N = 6; (3) intravenous infusion wit h 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 mu g/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 mu g/kg/min pl us ischemia (1 h ischemia, 2 h reperfusion), N = 6, A laser-Doppler flowmet er 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 a lone, OP-2507 significantly reduced the extent of microcirculatory and hemo dynamic derangement following ischemia-reperfusion. The changes of mean sys tolic arterial pressure (MSAP) following ischemia-reperfusion showed biphas ic alterations. OP-2507 at both doses significantly attenuated decreases in MSAP. OF-2507 lessened adherent leukocyte count and improved flow velocity in the sinusoids and postsinusoidal venules, OF-2507 at the dose of I mu g /kg/min reduced MDA (1.04 +/- 0.27 mu mol/g protein vs 2.64 +/- 0.59 mu mol /g protein in the ischemia and reperfusion group) and increased ATP levels (2.03 +/- 0.17 mu mol/g wet wt vs 0.73 +/- 0.21 mu mol/g wet wt in the isch emia and reperfusion group), while OF-2507 at a smaller dose (0.1 mu g/kg/m in) had lesser but significant effects on MDA and ATP alterations. Conclusi on. This study demonstrates that OP-2507 treatment of ischemia can ameliora te ischemia-reperfusion injury of the rat liver. (C) 1998 Academic Press.