An endothelin receptor antagonist ameliorates injuries of sinusoid lining cells in porcine liver transplantation - 08/09/11

Doi : 10.1016/S0002-9610(99)00107-5

Kiyoshi Fukunaga, MD ^a, Yasutsugu Takada, MD ^a,⁎, Gu Mei, MD ^a, Hideki Taniguchi, MD ^a, Kenichiro Seino, MD ^a, Kenji Yuzawa, MD ^a, Masaaki Otsuka, MD ^a, Takeshi Todoroki, MD ^a, Katsutoshi Goto, MD ^b, Katashi Fukao, MD ^a
^a Department of Surgery (KF, YT, GM, HT, KS, KY, MO, TT, KF), Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan
^b Department of Pharmacology (KG), Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan

^*Requests for reprints should be addressed to Yasutsugu Takada, MD, Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba City, Ibaraki 305-8575, Japan

Abstract

Background: TAK-044 is an endothelin receptor antagonist. Whether the agent has protective effects on liver graft injuries from non–heart-beating donors is unknown.

Methods: In donor pigs, cardiac arrest was induced by stopping the respirator. Forty-five minutes after cessation of the respirator, the liver was flushed with University of Wisconsin (UW) solution, preserved for 8 hours at 4°C, and transplanted orthotopically. The pigs were divided into two groups: a control group and a drug-treated group in which TAK-044 was given in the UW solutions (10 mg/L) and was administered to recipients (10 mg/kg body weight).

Results: TAK-044 treatment significantly increased recipient survival rate. After reperfusion of the graft, portal venous pressure and 15-minute retention rate of indocyanine green were significantly reduced in the drug-treated group. Electron microscopic findings indicated that TAK-044 attenuated endothelial cell injuries.

Conclusion: TAK-044 treatment improves the viability of livers harvested from non–heart-beating donors. The main effect of the agent is protection of endothelial cells from ischemia/reperfusion injuries.

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Plan

Materials and methods

Experimental design

Operative procedures

Blood chemical analysis

Measurement of portal venous pressure

Fifteen-minute retention rate of indocyanine green (ICGR15)

Histological examinations

Statistical analysis

Results

Postoperative survival

Serum liver enzymes and arterial lactate concentration

Portal venous pressure

ICGR15

Histological examinations

Comments

This work was supported in part by a grant from the Scientific Research Fund of the Ministry of Education, Japan, and a grant from the Japan Society for the Promotion of Science (JSPS-RFTF96I00202).

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Vol 178 - N° 1

P. 64-68 - juillet 1999 Retour au numéro

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An endothelin receptor antagonist ameliorates injuries of sinusoid lining cells in porcine liver transplantation - 08/09/11

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