Beneficial effect of thromboxane A2 synthetase inhibitor on cold-stored rat liver.
Prostanoids such as prostacyclin and thromboxane A2 have recently been suggested to play important roles in cold ischemia/reperfusion injury. The purpose of this study was to investigate the effect of thromboxane A2 synthetase inhibitor (OKY-046) on cold-stored livers of the rat using an ex vivo perfusion system. Addition of OKY-046 to preservation solution and the perfusate of livers stored cold (4 degrees C) in lactated Ringer's solution resulted in significantly lower glutamic pyruvic transaminase release (3.01 +/- 0.86 IU/g liver vs. 1.79 +/- 1.08 IU/g liver at 120 min after perfusion; P < 0.05), reduced perfusate ammonia levels (8.51 +/- 2.51 micrograms/dl/g liver vs. 3.62 +/- 1.71 micrograms/dl/g liver at 60 min; P < 0.05 and thereafter), lower perfusate taurocholate levels (0.63 +/- 0.10 vs. 0.18 +/- 0.05 at 15 min; P < 0.01 and thereafter), perfusate hyaluronic acid clearance (0.934 +/- 0.132 vs. 0.76 +/- 0.127 at 30 min; P < 0.05 and thereafter), and a reduced number of trypan blue-positive sinusoidal lining cells (50.1 +/- 9.9%; vs. 17.4 +/- 7.0%; P < 0.01). Histologically, the liver preserved for 6 hr in simple cold lactated Ringer's solution exhibited interstitial edema, various degrees of hepatocyte swelling, and sinusoidal stenosis, as well as dilatation, while the livers treated with OKY-046 demonstrated much less hepatocyte swelling, and change in sinusoidal width was nearly absent. We conclude that OKY-046 reduces post-preservation reoxygenation injury by protecting sinusoidal endothelial cells and hepatocytes.
Suehiro
T
T
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yanaga
K
K
Itasaka
H
H
Kishikawa
K
K
Shirabe
K
K
Sugimachi
K
K
D000410:Alanine Transaminase / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D015925:Cryopreservation; D006820:Hyaluronic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D009926:Organ Preservation; D010477:Perfusion; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013656:Taurocholic Acid / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D008689:Methacrylates; D011453:Prostaglandins; D013656:Taurocholic Acid; D000641:Ammonia; D006820:Hyaluronic Acid; D000410:Alanine Transaminase; D013930:Thromboxane-A Synthase; C034364:ozagrel