Protective effect of nitric oxide induced by ischemic preconditioning on reperfusion injury of rat liver graft

Abstract

AIM: 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 Nω-nitro-L-arginine methyl ester abolished the protective effect of IP.CONCLUSION: 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 JP, Tu B, Wang W, Peng Y, Li SB, Yan LN. Protective effect of nitric oxide induced by ischemic preconditioning on reperfusion injury of rat liver graft.

What Should Be the Ideal Time for Ischemic Preconditioning in a Laparoscopic Rat Model?

“…In the literature, there were several studies using different IP application times, such 5-10 minutes of Pp, followed by 5-10 minutes of deflation, but none of them compare the different application times. [31][32][33] In the present study, a comparison of the IP 5-minutes and IP 10-minutes groups, in terms of oxidative stress response, demonstrated that there was no statistical difference between the IP groups. Consequently, our findings suggest that 5 minutes of an IP period is as effective as 10 minutes of an IP period in preventing the harmful effects of Pp in the laparoscopic rat model.…”

Delayed Energy Protection of Ischemic Preconditioning on Hepatic Ischemia/Reperfusion Injury in Rats

“…Endothelial NOS is present in liver endothelial cells, and responsible for the NO production in early preconditioning [30] . iNOS is present in all liver cell types and the source of NO in late preconditioning [31] . NO produced by endothelial cells play an important role in maintaining the caliber of blood vessels and its reduced release is one of the earliest signs of reperfusion induced by endothelial dysfunction.…”

The nitric oxide pathway – evidence and mechanisms for protection against liver ischaemia reperfusion injury

“…In addition, eNOS‐derived NO has also been shown to decrease hepatic aggregation of neutrophils . In a separate animal OLT model, it was shown that endogenous NO reduces the rise of cold IR‐induced TNF‐α expression . Moreover, endogenous NO also limits the rise and inhibits the action of another pro‐inflammatory cytokine, IL‐1α, in reduced‐size OLT, and in parallel, decreases hepatic tissue oxidative damage .…”