The portosystemic shunt protects liver against ischemic reperfusion injury.

Sankary HN, Yin DP, Chong AS, Ma LL, Blinder L, Shen JK, Foster P, Liu LP, Li C, Williams JW
Transplantation. 1999 68 (7): 958-63

PMID: 10532534 · DOI:10.1097/00007890-199910150-00010

BACKGROUND - The goal of this study was to characterize the importance of splanchnic viscera in liver ischemic reperfusion injury and to enhance the tolerance of liver to warm ischemia injury with portosystemic shunt.

METHODS - The hepatic blood flow of male Sprague Dawley rats was subjected to 45, 60, 120, and 150 min liver warm ischemia with or without portosystemic shunt (splenic-caval shunt). The production of tumor necrosis factor a (TNFa), nuclear factor-kappaB activation, inducible NO synthase (iNOS) expression, and apoptosis were examined.

RESULTS - A total of 67% of rats with 45 min liver warm ischemia (n=6) and 100% of rats with 60 min liver warm ischemia (n=6) died within 1 day. However, all rats with 120 min (n=8) liver warm ischemia in splenic-caval shunt group survived for over 1 day, 6/8 for over 3 days, and 5/8 for over 5 days without significant histological changes of the liver. Serum tumor necrosis factor levels in liver warm ischemic rats were increased, This increase was significantly reversed after portosystemic shunt. After challenge with lipopolysaccharide (1 mg/kg, p.v.), naive rats survived for over 5 days (n=4) with the peak value of rat tumor necrosis factor (240 pg/ml) at 90 min. In contrast, all rats died within one day (n=5) with the peak value of rat tumor necrosis factor a (465 pg/ml) at 45 min after administration of lipopolysaccharide in the rats with liver warm ischemia plus splenic-caval shunt. iNOS expression and nuclear factor-kappaB activation were very strongly increased in the hepatocytes after liver warm ischemia with portosystemic shunt, compared with liver ischemia without portosytemic shunt.

CONCLUSIONS - We conclude that the splanchnic viscera can contribute to liver ischemic reperfusion injury. Portosystemic shunt enhances the tolerance of liver to warm ischemia through the protective role of iNOS and nuclear factor-kappaB (NF-kappaB).

MeSH Terms (17)

Animals Enzyme Activation Hot Temperature Lipopolysaccharides Liver Liver Circulation Male NF-kappa B Nitric Oxide Synthase Nitric Oxide Synthase Type II Portasystemic Shunt, Surgical Rats Rats, Sprague-Dawley Reperfusion Injury RNA, Messenger Splanchnic Circulation Tumor Necrosis Factor-alpha

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