Pretreatment with Soluble Thrombomodulin Prevents Intrasinusoidal Coagulation and Liver Dysfunction following Extensive Hepatectomy in Cirrhotic Rats

Toshimi Kaido; Akira Yoshikawa; Shin-ichi Seto; Shoji Yamaoka; Hiroaki Furuyama; Shigeki Arii; Yasuo Takahashi; Masayuki Imamura

doi:10.1055/s-0037-1614380

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(04): 1302-1306
DOI: 10.1055/s-0037-1614380

Review Article

Schattauer GmbH

Pretreatment with Soluble Thrombomodulin Prevents Intrasinusoidal Coagulation and Liver Dysfunction following Extensive Hepatectomy in Cirrhotic Rats

Authors

Toshimi Kaido

¹From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
Akira Yoshikawa

¹From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
Shin-ichi Seto

¹From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
Shoji Yamaoka

¹From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
Hiroaki Furuyama

¹From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
Shigeki Arii

¹From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,
Yasuo Takahashi

²Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan
Masayuki Imamura

¹From the Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto,

Abstract

Summary

The major cause of posthepatectomy liver dysfunction is supposed to be microcirculatory disturbance caused by imbalance of intrasinusoidal coagulation equilibrium. Thrombomodulin (TM) is a potent anticoagulant expressed on the endothelial cell surface that regulates the coagulation system by binding thrombin and accelerating the thrombin-catalyzed activation of protein C. Therefore, we examined the effect of soluble TM purified from human urine (UTM) on intrasinusoidal coagulation in cirrhotic rats. Dimethylnitrosamine-induced cirrhotic rats underwent 70% hepatectomy and received endotoxin 48 h after. UTM or vehicle alone was intravenously administered to each rat 30 min before endotoxin injection. UTM treatment attenuated the increases in cytosolic enzymes and serum hyaluronic acid level. The UTM supply improved the survival rate of the rats at 12 h after endotoxin challenge. Histologically, intrasinusoidal fibrin depositions and massive hepatocellular necrosis observed in control rats were scarcely found in UTM-treated rats. Immunohistochemical examination revealed that marked TM stains in sinusoidal endothelial cells were well preserved in UTM-treated rats. In conclusion, UTM administration prevented intrasinusoidal fibrin depositions and attenuated posthepatectomy liver dysfunction in cirrhotic rats.

Full Text

References

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