EVIDENCE FOR THE INVOLVEMENT OF OXYGEN-DERIVED FREE-RADICALS IN ISCHEMIA-REPERFUSION INJURY

Six patients undergoing vascular reconstructive surgery were examined for evidence of oxygen-derived free radical (OFR) damage to the protein, immunoglobulin G (IgG). OFR damage was determined as an increase in the fluorescence (ex 360 nm em 454 nm) to ultraviolet absorption (280 nm) ratio of IgG, representing N-Formyl kynurenine and other as yet unidentified fluorophores. The IgG ratio was found to increase slightly during ischaemia and to undergo marked elevation upon reperfusion (275 +/- 405% baseline value at 40 min post-clamp; mean +/- sd). A high ratio was maintained post-reperfusion, even after 60 min reperfusion. Determination of thromboxane B2, (TXB2),leukotriene B4, (LTB4) and 6-keto prostaglandin Flalpha, (PGF1a), revealed a decrease in their concentrations during ischaemia and a transient, marked increase on reperfusion. Only TXB2 concentrations were found to correlate with the IgG ratio (negative correlation, p < 0.05). No correlation was observed between von Willebrand antigen factor, a marker of endothelial cell damage and fluorescent IgG ratio. However, levels of the factor increased slightly during ischaemia and more sharply upon reperfusion. These preliminary results therefore suggest that a more likely source of the OFRs responsible for IgG damage is endothelial cell xanthine oxidase, rather than cyclo-oxygenase or lipoxygenase.