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

AbstractBACKGROUND:
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.
AuthorsH M Chen, M F Chen, M H Shyr
JournalThe Journal of surgical research (J Surg Res) Vol. 80 Issue 2 Pg. 333-8 (Dec 1998) ISSN: 0022-4804 [Print] United States
PMID9878334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 1998 Academic Press.
Chemical References
  • Malondialdehyde
  • OP 2507
  • Adenosine Triphosphate
  • Epoprostenol
Topics
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Blood Flow Velocity (drug effects)
  • Blood Pressure (drug effects)
  • Disease Models, Animal
  • Energy Metabolism (drug effects)
  • Epoprostenol (administration & dosage, analogs & derivatives, pharmacology)
  • Infusions, Intravenous
  • Leukocytes (drug effects, physiology)
  • Lipid Peroxidation (drug effects)
  • Liver (blood supply, drug effects, injuries)
  • Liver Circulation (drug effects)
  • Male
  • Malondialdehyde (metabolism)
  • Microcirculation (drug effects)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (drug therapy, metabolism, physiopathology)
  • Time Factors

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