Protective effect of human urinary thrombomodulin on ischemia- reperfusion injury in the canine liver.
This study was performed to determine whether human urinary soluble thrombomodulin plays a role in liver ischemia-reperfusion injury. Liver ischemia was induced in two groups of dogs. Group 1 was exposed to 60 min ischemia, and group 2 was exposed to 60 min ischemia after preischemic administration of human urinary soluble thrombomodulin. In group 1, the thrombin-antithrombin complex and hyaluronic acid were significantly elevated after ischemia, compared with the preischemic values. While liver issue blood flow and the plasmin-alpha(2)-plasmin inhibitor complex significantly decreased, AST, ALT and m-AST dramatically increased after reperfusion. In group 2, the increase in the thrombin-antithrombin complex and hyaluronic acid was significantly suppressed, and AST, ALT and liver tissue blood flow significantly improved, compared with group 1. Histologically, in group 2, the hepatic tissue structure, including endothelial cells, was relatively intact. These findings suggest that administration of thrombomodulin inhibits endothelial cell injury and coagulopathy and offers protection from liver ischemia-reperfusion injury.
Kaneko
H
H
Second Department of Surgery, Toho University School of Medicine, Tokyo, Japan. hironori@med.toho-u.ac.jp
Joubara
N
N
Yoshino
M
M
Yamazaki
K
K
Mitumaru
A
A
Miki
Y
Y
Satake
H
H
Shiba
T
T
D000818:Animals; D001772:Blood Cell Count; D001780:Blood Coagulation Tests; D001794:Blood Pressure; D004285:Dogs; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000201:enzymology; D008102:Liver Circulation / Q000187:drug effects*; D008854:Microscopy, Electron; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018180:Thrombomodulin / Q000302:isolation & purification / Q000627:therapeutic use*; D014556:Urine / Q000737:chemistry
D018180:Thrombomodulin; D006820:Hyaluronic Acid