ATTENUATION OF ISCHEMIA-REPERFUSION INJURY BY HUMAN THIOREDOXIN

Background - Active oxygen species are thought to play a part in ischa emia reperfusion injury. The ability of a novel agent, human thioredox in (hTRX), to attenuate lung damage has been examined in a rat model o f ischaemia reperfusion injury. Methods - Twenty eight animals were st udied. At thoracotomy the left main bronchus and the left main pulmona ry artery were clamped for 75 minutes and the lung was then reperfused for 20 minutes. Phosphate buffered saline was administered intravenou sly to nine control animals and hTRX (30 mu g/g body weight) was given intravenously to another group of nine animals. Two experiments were carried out. The first (Exp 1) was a time matched pair experiment (fiv e treated, five controls), and the second (Exp 2) was performed under controlled conditions (four treated, four controls; temperature 25 deg rees C, humidity 65%). In another 10 non-ischaemic rats and those in E xp 1 biochemical measurements of lipid peroxide, superoxide dismutase, and glutathione peroxide levels were performed. Results - In both exp eriments rats perfused with hTRX survived longer than controls. In Exp 1 the arterial oxygen tension (PaO2) on air in the hTRX group was hig her at 20 minutes than at one minute after reperfusion. In Exp 2 PaO2 at 20 minutes was higher in the hTRX group than in the controls. Lipid peroxide, superoxide dismutase, and glutathione peroxide levels in th e control group were higher than in the hTRX group and in the non-isch aemic groups. Histological examination showed less thickening and oede ma of the alveolar walls in the hTRX group than in controls. Conclusio ns - These results suggest that hTRX is effective as a radical scaveng er and can limit the extent of ischaemia reperfusion injury of the lun gs of experimental animals.