Prolonged ischemia is associated with more pronounced rejection in the lung allograft

Previously it was found that ischemia-reperfusion injury in a left lung autotransplantation model could be a minor inducer of major histocompatibility complex (MHC) class II antigen expression. Thus, we hypothesized that prolonged ischemic times may result in increased expression of MHC class II antigens and predispose the lungs to the development of acute rejection early after transplantation.

Twenty conditioned dogs underwent single left lung allotransplantation. Donor lungs were subjected to 4 or 24 hours (n = 10 each) of cold ischemia. Open lung biopsies, bronchoalveolar lavage fluid, and blood samples were taken preoperatively and at various intervals up to 1 week after transplantation. Lung biopsy specimens were examined histologically for MHC class II expression and graded for acute rejection. Bronchoalveolar lavage fluid and plasma were analyzed for cytokines interleukin-2 and interferon-gamma.

In the 4-hour ischemia group, there was mild diffuse staining of the bronchial epithelium and cellular infiltrate for MHC class II antigens after 1 week with subsequent grade 1-2 rejection. In the 24-hour ischemia group, MHC expression after 1 week revealed strong diffuse staining of bronchial epithelium, vascular endothelium, and cellular infiltrates with a significantly higher grade of rejection. Interleukin-2 and interferon-gamma significantly increased in BAL fluid early after transplantation in both groups.

Ischemic injury may predispose the lung allograft to the development of acute rejection, in part, through the upregulation of MHC class II antigen expression and the local release of cytokines.