Prostaglandin E1 resuscitates hepatic organic anion transport independent of its hemodynamic effect after warm ischemia.
Prostaglandin E1 (PGE1) is a promising agent against ischemic liver damage, but direct evidence of the benefit to intrinsic hepatocyte function has been lacking. We demonstrate here that organic anion transport can be supported by treatment with PGE1 even at a lower dose which does not affect hepatic microcirculation in rabbits with liver inflow occlusion. Near-infrared spectroscopy was applied to directly measure hepatic clearance of indocyanine green (ICG), an exogenous organic anion, and to estimate microcirculation as measured by oxygen saturation and the content of hemoglobin in the sinusoid. Also, morphological changes in microtubules, the cytoskeleton which is known to be associated with organic anion transport, and energy status, as measured by adenine nucleotide levels, were observed. ICG removal rate in hepatocytes decreased significantly from 0.100 +/- 0.018 to 0.027 +/- 0.019 min-1 (mean +/- SD, P < 0.01) by 60-min warm ischemia, whereas the value increased to 0.082 +/- 0.030 min-1 (P < 0.05) when PGE1 was given at a dose of 0.05 microgram/kg/min. The treated livers also showed early reorganization of microtubules, as well as amelioration of ATP resynthesis after reperfusion. However, there were no significant differences in intraoperative changes in oxygen saturation and the content of hemoglobin in the sinusoid between PGE1-treated and untreated groups, indicating that the influence of PGE1 at this dose on hemodynamic changes is not considerable. These results indicate that PGE1 resuscitates an inherent hepatocyte function of organic anion transport on reperfusion after warm ischemia and suggest that the benefit could be attributed solely to direct action on hepatocytes.
Shinohara
H
H
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Japan.
Tanaka
A
A
Fujimoto
T
T
Kanazawa
A
A
Satoh
S
S
Hatano
E
E
Yamaoka
Y
Y
D000227:Adenine Nucleotides / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D006439:Hemodynamics / Q000502:physiology*; D007208:Indocyanine Green / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008102:Liver Circulation / Q000502:physiology; D008297:Male; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000737:chemistry / Q000648:ultrastructure; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D000227:Adenine Nucleotides; D014404:Tubulin; D014665:Vasodilator Agents; D000527:Alprostadil; D007208:Indocyanine Green