Circulating xanthine oxidase and neutrophil activation during human liver transplantation.

Abstract

Oxygen free radicals, generated by xanthine oxidase (XO) and activated leukocytes, are involved in reperfusion injury in experimental liver transplantation. The roles of XO and neutrophil activation during reperfusion in clinical liver transplantation were studied. In 10 patients undergoing liver transplantation, we assessed plasma concentrations of circulating XO by enzyme-linked immunosorbent assay (ELISA), the purine metabolites hypoxanthine, xanthine, and urate by high-performance liquid chromatography, lactoferrin by ELISA, and malondialdehyde fluorometrically up to 48 hours postoperatively. During reperfusion after portal vein declamping, elevated plasma concentrations of XO (52.1 ng/mL [range, 8.0-440.1]), hypoxanthine (81.62 micromol/L [48.2-108.7]), xanthine (21.01 micromol/L [8.7-22.3]), and lactoferrin (532.6 ng/mL [370.4-1326.6]) were observed compared with the preoperative levels (0 ng/mL [0-12], 1.88 micromol/L [0.62-3.15], 0.95 micromol/L [0-0.41], and 164.3 ng/mL [73.7-334.1], respectively; all P < 0.05). No changes occurred in urate or malondialdehyde. After portal vein declamping, XO, hypoxanthine, and xanthine levels were substantially greater in the hepatic than portal vein (all P < 0.05). Marginal transhepatic differences occurred in lactoferrin. Reperfusion during liver transplantation is associated with liberation of xanthine oxidase, hypoxanthine, and xanthine from the liver into the circulation. During reperfusion, intravascular neutrophil activation takes place in the hepatic circulation.