Compromised antioxidant status and persistent oxidative stress in lung transplant recipients

Oxidative stress may be a key feature, and hence important determinant, of tissue injury and allograft rejection in lung transplant recipients. To inv estigate this, we determined the antioxidant status (urate, ascorbate, thio ls and a-tocopherol) and lipid peroxidation status (malondialdehyde) in bro nchoalveolar lavage (BAL) fluid and blood serum of 19 consecutive lung tran splant recipients 2 weeks and 1, 2, 3, 6, and 12 months post-surgery. BAL f luid and blood samples from 23 control subjects and blood from 8 patients t wo days before transplantation were obtained for comparison. Before surgery , the antioxidant status of patients was poor as serum ascorbate and total thiol concentrations were significantly (p < 0.05) lower than control subje cts. Two weeks post-surgery, ascorbate and total thiol concentrations were still low and urate concentrations had fallen compared to control subjects (p < 0.01). At this time, BAL fluid urate concentration was higher (p < 0.0 1), ascorbate concentration was lower (p < 0.01) and reduced glutathione co ncentrations were similar to control subjects. MDA, a product of lipid pero xidation, was higher (p < 0.01) in both BAL fluid and serum obtained from t ransplant patients compared to control subjects. During the first 12 months post-surgery, little improvement in antioxidant status or extent of lipid peroxidation was seen in transplant recipients. Regression analysis indicat ed no difference in serum or BAL fluid antioxidant status in patients with acute rejection compared to those without. In conclusion, lung transplant r ecipients have a compromised antioxidant status before surgery and it remai ns poor for at least the first year following the operation. In addition, t hese patients have elevated MDA concentrations in both their lung lining fl uid and blood over most of this time. Oxidative stress is not, however, a s ufficiently sensitive endpoint to predict tissue rejection in this group.