Evidence for the involvement of oxygen-derived free radicals in ischaemia-reperfusion injury.
Six patients undergoing vascular reconstructive surgery were examined for evidence of oxygen-derived free radical (ORF) 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 F1 alpha, (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.
Vascular Unit, Basingstoke District Hospital, Basingstoke, UK.
A
A
Ward
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A
McBurney
J
J
Lunec
D000368:Aged; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007511:Ischemia; D007866:Leg / Q000098:blood supply; D007975:Leukotriene B4 / Q000097:blood; D008875:Middle Aged; D011460:Prostaglandins F / Q000097:blood; D015427:Reperfusion Injury / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000097:blood; D014656:Vascular Surgical Procedures; D014841:von Willebrand Factor / Q000032:analysis
D005609:Free Radicals; D007074:Immunoglobulin G; D011460:Prostaglandins F; D014841:von Willebrand Factor; D007975:Leukotriene B4; D013929:Thromboxane B2; C100006:prostaglandin F1