Involvement of thromboxane A2-thromboxane A2 receptor system of the hepatic sinusoid in pathogenesis of cold preservation/reperfusion injury in the rat liver graft.
This study was designed to investigate the possible involvement of the thromboxane A2 (TXA2)-TXA2 receptor (TXA2R) system of the hepatic sinusoid in cold preservation/reperfusion injury in liver grafts. Rat livers were preserved in cold University of Wisconsin solution for either 6 or 24 hr. The number of TXA2Rs in sinusoidal endothelial cells isolated from 0-, 6-, and 24-hr preserved liver specimens was 22.50 +/- 1.80 x 10(3)/cell, 12.66 +/- 1.00 x 10(3)/cell, and 4.17 +/- 0.65 x 10(3)/cell, respectively. Kd and Bmax at 0 hr, 6 hr, and 24 hr of preservation were 8.54 +/- 1.26 nM and 37.34 +/- 3.01 fmol/10(6) cells, 7.08 +/- 1.14 nM and 12.66 +/- 1.00 fmol/10(6) cells, and 1.91 +/- 0.10 nM and 3.88 +/- 0.59 fmol/10(6) cells, respectively. The administration of OKY-046 (inhibitor of TXA2 synthesis) to the University of Wisconsin solution suppressed this reduction in TXA2R number. Furthermore, the concentration of TXA2 in hepatic sinusoid was decreased by OKY-046. In a reperfusion experiment, liver tissue preserved for 24 hr exhibited a higher reperfusion pressure, and effluent levels of both aspartate aminotransferase and lactate dehydrogenase were markedly elevated. The addition of OKY-046 to the preservation solution, however, prevented the rise in reperfusion pressure almost completely and the increase in effluent enzyme levels. This study showed that the TXA2Rs in sinusoidal endothelial cells were internalized through binding with TXA2 during cold preservation, causing activation of the TXA2-TXA2R system. This activation apparently induces an increase in reperfusion pressure, possibly due to sinusoidal contraction, resulting in microcirculatory disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishiguro
S
S
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Arii
S
S
Monden
K
K
Fujita
S
S
Nakamura
T
T
Niwano
M
M
Harada
T
T
Ushikubi
F
F
Narumiya
S
S
Imamura
M
M
D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D015925:Cryopreservation; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000098:blood supply* / Q000166:cytology; D016031:Liver Transplantation / Q000502:physiology*; D008689:Methacrylates / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D009926:Organ Preservation; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000502:physiology*; D015427:Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology* / Q000517:prevention & control; D013928:Thromboxane A2 / Q000378:metabolism / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D008689:Methacrylates; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D013930:Thromboxane-A Synthase; C034364:ozagrel