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The cytoprotective effects of addition of activated protein C into preservation solution on small‐for‐size grafts in rats
Author(s) -
Kuriyama Naohisa,
Isaji Shuji,
Hamada Takashi,
Kishiwada Masashi,
Ohsawa Ichiro,
Usui Masanobu,
Sakurai Hiroyuki,
Tabata Masami,
Hayashi Tatsuya,
Suzuki Koji
Publication year - 2010
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21923
Subject(s) - medicine , nitric oxide , reperfusion injury , transplantation , nitric oxide synthase , protein c , pharmacology , apoptosis , liver transplantation , tumor necrosis factor alpha , kupffer cell , ischemia , immunology , biochemistry , chemistry
Small‐for‐size liver grafts are a serious obstacle for partial orthotopic liver transplantation. Activated protein C (APC), a potent anticoagulant serine protease, is known to have cell‐protective properties due to its anti‐inflammatory and antiapoptotic activities. This study was designed to examine the cytoprotective effects of a preservation solution containing APC on small‐for‐size liver grafts, with special attention paid to ischemia‐reperfusion injury and shear stress in rats. APC exerted cytoprotective effects, as evidenced by (1) increased 7‐day graft survival; (2) decreased initial portal pressure and improved hepatic microcirculation; (3) decreased levels of aminotransferase and improved histological features of hepatic ischemia‐reperfusion injury; (4) suppressed infiltration of neutrophils and monocytes/macrophages; (5) reduced hepatic expression of tumor necrosis factor α and interleukin 6; (6) decreased serum levels of hyaluronic acid, which indicated attenuation of sinusoidal endothelial cell injury; (7) increased hepatic levels of nitric oxide via up‐regulated hepatic endothelial nitric oxide synthesis expression together with down‐regulated hepatic inducible nitric oxide synthase expression; (8) decreased hepatic levels of endothelin 1; and (9) reduced hepatocellular apoptosis by down‐regulated caspase‐8 and caspase‐3 activities. These results suggest that a preservation solution containing APC is a potential novel and safe product for small‐for‐size liver transplantation, alleviating graft injury via anti‐inflammatory and antiapoptotic effects and vasorelaxing conditions. Liver Transpl 16:1–11, 2010. © 2009 AASLD.