Protective effect of nitric oxide induced by ischemic preconditioning on reperfusion injury of rat liver graft.
OBJECTIVE
Ischemic preconditioning (IP) is a brief ischemic episode, which confers a state of protection against the subsequent long-term ischemia-reperfusion injuries. However, little is known regarding the use of IP before the sustained cold storage and liver transplantation. The present study was designed to evaluate the protective effect of IP on the long-term preservation of liver graft and the prolonged anhepatic-phase injury.


METHODS
Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation. All livers underwent 10 min of ischemia followed by 10 min of reperfusion before harvest. Rat liver transplantation was performed with the portal vein clamped for 25 min. Tolerance of transplanted liver to the reperfusion injury and liver damage were investigated. The changes in adenosine concentration in hepatic tissue and those of nitric oxide (NO) and tumor necrosis factor (TNF) in serum were also assessed.


RESULTS
Recipients with IP significantly improved their one-week survival rate and liver function, they had increased levels of circulating NO and hepatic adenosine, and a reduced level of serum TNF, as compared to controls. Histological changes indicating hepatic injuries appeared improved in the IP group compared with those in control group. The protective effect of IP was also obtained by administration of adenosine, while blockage of the NO pathway using Nomega-nitro-L-arginine methyl ester abolished the protective effect of IP.


CONCLUSIONS
IP appears to have a protective effect on the long-term preservation of liver graft and the prolonged anhepatic-phase injuries. NO may be involved in this process.
Gong
Jian-Ping
JP
Department of General Surgery, Huaxi Hospital, Sichuan University, Chengdu 610041, Shichuan Province, China. gongjianping11@hotmail.com
Tu
Bing
B
Wang
Wei
W
Peng
Yong
Y
Li
Shou-Bai
SB
Yan
Lu-Nan
LN
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D006085:Graft Survival / Q000502:physiology*; D019194:Ischemic Preconditioning; D008099:Liver / Q000473:pathology / Q000502:physiology; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000241:Adenosine