N-ACETYLCYSTEINE FAILED TO IMPROVE EARLY MICROCIRCULATORY ALTERATIONSOF THE RAT-LIVER AFTER TRANSPLANTATION

The application of radical scavengers reduces reperfusion injury of li ver grafts despite the natural occurrence of cellular defense mechanis ms enabling the cell to tolerate moderate oxidant stress without furth er cell damage. The glutathione peroxidase mechanism of the liver serv es to reduce hydroxyl radical-induced lipid peroxidation by releasing reduced glutathione from intracellular stores. There is evidence that the application of cysteine-providing aminoacids for glutathione synth esis could maintain or even increase liver glutathione. Therefore, the purpose of this study was to evaluate the effect of N-acetylcysteine (NAG) on oxidative stress-induced reperfusion injury after liver trans plantation. This was done by applying intravital microscopy. Livers fr om female Sprague-Dawley rats weighing 220-260 g were stored for 20 h in University of Wisconsin (UW) solution and transplanted orthotopical ly using the cuff technique. Donors were given 150 mg/kg body weight N AC i. v. or placebo in a blind, random fashion 6 h prior to harvesting , followed by two injections of 50 mg/kg body weight, 4 and 2 h before explantation. In additional experimental groups, recipients were give n a bolus of 83 mg/kg body weight NAC or placebo at the beginning of t he recipient operations, 1 min prior to reperfusion, and 60 min after surgery. Ninety minutes after transplantation, intravital microscopy w as applied and five liver lobules were recorded for 30 s after injecti on of acridine orange, a fluorescent leukocyte marker. Sinusoidal perf usion, sinusoidal width, and leukocyte adhesion, as well as reduced an d oxidized glutathione, were determined in all livers. Neither microci rculatory disturbance nor leukocyte adhesion was less, nor was the liv er glutathione in the recipient groups pretreated or treated with NAC greater than that in rats receiving the placebo. Moreover, liver gluta thione was significantly decreased in livers from donors pretreated wi th NAG. In conclusion, the application of NAC as a pretreatment for do nors and as treatment for recipients, respectively, failed to reduce e arly microvascular failure after liver transplantation.