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 protei n, 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 u nidentified fluorophores. The IgG ratio was found to increase slightly during ischaemia and to undergo marked elevation upon reperfusion (27 5 +/- 405% baseline value at 40 min post-clamp; mean +/- sd). A high r atio was maintained post-reperfusion, even after 60 min reperfusion. D etermination of thromboxane B2, (TXB2),leukotriene B4, (LTB4) and 6-ke to prostaglandin Flalpha, (PGF1a), revealed a decrease in their concen trations during ischaemia and a transient, marked increase on reperfus ion. Only TXB2 concentrations were found to correlate with the IgG rat io (negative correlation, p < 0.05). No correlation was observed betwe en von Willebrand antigen factor, a marker of endothelial cell damage and fluorescent IgG ratio. However, levels of the factor increased sli ghtly during ischaemia and more sharply upon reperfusion. These prelim inary results therefore suggest that a more likely source of the OFRs responsible for IgG damage is endothelial cell xanthine oxidase, rathe r than cyclo-oxygenase or lipoxygenase.