Gaseous oxygen for hypothermic preservation of predamaged liver grafts: fuel to cellular homeostasis or radical tissue alteration?
Gaseous persufflation with molecular oxygen during cold storage has recently been discussed as an adjunct in the preservation of predamaged livers from non-heart-beating donors. In this study, the actual importance of an antioxidant medication prior to oxygen persufflation was investigated for the first time. Rat livers were excised 60 min after cardiac arrest of the donor, flushed with UW, and stored at 4 degrees C for 24 h. Gaseous oxygen, applied to the livers during the storage period via the caval vein at a pressure limited to 18 mm Hg, was only effective in improving hepatic viability upon reperfusion when antioxidants (superoxide dismutase (SOD) or n-acetylcysteine) were added to the UW rinse solution. Either drug prevented an increase in free radical mediated lipid peroxidation. Acetylcysteine but not SOD also counteracted the phosphorylation of Ikappab and thus the transcriptional activation of NFkappab. Poor results after oxygen persufflation without antioxidants may hence be explained by concomitant free radical induced tissue alterations upon introduction of molecular oxygen into ischemically predamaged organs.
Minor
T
T
Surgical Research Division, University of Bonn, Bonn, 53127, Germany.
Kötting
M
M
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D015687:Cell Hypoxia; D015925:Cryopreservation / Q000379:methods*; D005609:Free Radicals; D005740:Gases; D006706:Homeostasis; D007262:Infusions, Intravenous; D007327:Insufflation; D007511:Ischemia / Q000517:prevention & control; D008099:Liver / Q000098:blood supply / Q000187:drug effects*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D018384:Oxidative Stress; D010100:Oxygen / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology; D014019:Tissue Donors; D009927:Tissue and Organ Procurement; D014682:Vena Cava, Inferior
D000975:Antioxidants; D005609:Free Radicals; D005740:Gases; D013482:Superoxide Dismutase; D010100:Oxygen; D000111:Acetylcysteine