S-nitroso-N-acetylcysteine: a promising drug for early ischemia/reperfusion injury in rat liver.

BACKGROUND/AIMS: Ischemia-reperfusion (I/R) injury is among the major causes of poor graft function early after liver transplantation that adversely influences patient survival. A variety of mediators have been implicated in the pathogenesis of I/R vascular injury, including nitric oxide (NO). Because of the beneficial effects of NO during preconditioning and reperfusion, strategies to prevent or ameliorate I/R injury through the stimulation of hepatic NO production are an area of significant clinical interest. We evaluated the role of S-nitroso-N-acetylcysteine (SNAC) as an NO donor in the prevention of liver I/R injury in an animal model. METHODS: Adult male Wistar rats were randomly assigned to 3 experimental groups containing 5 animals each: the University of Wisconsin (UW) solution group; SNAC solution group; and SNAC-containing UW solution (SNAC+UW) group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were determined in samples of the cold storage solution at 2, 4, and 6 hours of preservation. After 6 hours of cold storage, We applied a 15-minute reperfusion period. Thereafter, the reperfusion was interrupted with blood samples obtained to measure AST, ALT, LDH, and thiobarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis, and to determine of TBARS, catalase, and glutathione levels. RESULTS: During cold preservation, AST and LDH were significantly lower among the SNAC than the UW group or the SNAC+UW group (P = .004 and P = .03, respectively). ALT was comparable among the groups (P = .3). After reperfusion, serum levels of AST, ALT, and LDH, as well as of hepatic TBARS and catalase showed no differences among the groups. Glutathione concentration was lower in the SNAC and SNAC+UW group (P < .001) compared with the UW group. We did not observe histologic signs of preservation injury. CONCLUSION: The SNAC solution showed a greater protective effect to preserve rat livers during cold storage, but it was comparable with UW.

Hepatic reperfusion in rats: a new model with portal arterialization in studying early ischemia-reperfusion injury.

Isolated liver perfusion has been used to evaluate the beneficial effects of several agents. In the present study, we developed a model using a recipient rat to reperfuse harvested livers in an ex situ, in vivo recirculating system. A total of 25 reperfusion procedures using adult male Wistar rats as donors and recipients were done. The preservation of the livers was performed with University of Wisconsin solution for 6 hours. Thereafter, the liver was reperfused with blood from another rat. We believe that the model presented herein offers an alternative method to evaluate early hepatocellular damage or hepatic microcirculation.