The mechanism of hepatic graft protection against reperfusion injury by prostaglandin E1.
The purpose of this study was to evaluate the effect of prostaglandin E1 (PGE1) on protecting against hepatic endothelial cell damage and increasing graft viability after cold preservation and reperfusion, using an isolated perfused rat liver (IPRL) model. The grafts were divided into three groups, according to the cold preservation time and PGE1 administration, namely: 4h preservation (group 1, n = 9), 6h preservation (group 2, n = 9), and 6h preservation followed by PGE1 infusion (group 3, n = 9). After cold storage, the grafts were put on the recirculating IPRL system, then reperfused for 120 min at 37 degrees C with oxygenated Krebs-Henseleit buffer containing hyaluronic acid (HA). To examine the function of the sinusoidal endothelial cells and hepatocytes, serial measurements of HA, tumor necrosis factor-alpha (TNFalpha), thromboxane B2 (TXB2), acid phosphatase, and conventional parameters in the perfusate were made. After perfusion, the trypan blue exclusion test was performed to assess the presence of any microscopic sinusoidal lining cell damage. In group 3, the bile output and HA clearance were significantly greater, while glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, TNFalpha, TXB2, and acid phosphatase in the perfusate were significantly lower than in group 2. Histologically, less endothelial cell damage and hepatocyte damage than in group 2 was also confirmed. These results therefore suggest that the improvement of hepatic graft viability by PGE1 administration is mainly due to sinusoidal endothelial cell protection.
Itasaka
H
H
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Suehiro
T
T
Wakiyama
S
S
Yanaga
K
K
Shimada
M
M
Sugimachi
K
K
D000135:Acid Phosphatase / Q000032:analysis; D000410:Alanine Transaminase / Q000032:analysis; D000527:Alprostadil / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D015925:Cryopreservation; D004727:Endothelium / Q000166:cytology / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects; D006820:Hyaluronic Acid / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D006820:Hyaluronic Acid; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000135:Acid Phosphatase; D000527:Alprostadil