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 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.


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.


CONCLUSIONS
This study demonstrates that OP-2507 treatment of ischemia can ameliorate ischemia-reperfusion injury of the rat liver.
Chen
H M
HM
Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China.
Chen
M F
MF
Shyr
M H
MH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007262:Infusions, Intravenous; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects* / Q000293:injuries; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
D008315:Malondialdehyde; C049453:OP 2507; D000255:Adenosine Triphosphate; D011464:Epoprostenol