Cyclosporin A as the initial immunosuppressive agent for canine lung transplantation: Short-and long-term assessment of rejection phenomena

Cyclosporin A (Cy A) was evaluated as the initial immunosuppressive agent for lung transplantation in unmatched mongrel dogs. Rejection phenomena were assessed by plain chest roentgenograms, histology, radionuclide ventilation-perfusion scans, and by the level of lectin-mediated lymphocyte cytotoxicity in cells obtained by bronchoalveolar lavage. Two groups of lung allograft recipients were studied. One group was treated with Cy A alone and the other was treated with Cy A and a short course of azathioprine (AZA) therapy (2 mg/kg/day for 14 days). Recipient survival and the nature and severity of rejection phenomena were similar in the two groups. Two morphologically and functionally distinct patterns of rejection occurred with similar frequency in Cy A and Cy A-AZA-treated lung allograft recipients. The first pattern was characterized by extensive changes in plain chest roentgenograms, the presence of interstitial, perivascular, and alveolar mononuclear cell infiltrates in histological sections, both ventilation and perfusion abnormalities on lung scans, and relatively high levels of lectin-mediated T cell cytotoxicity. The second pattern of rejection was characterized by minimal changes on chest films, histological findings limited to perivascular mononuclear cell infiltrates, relatively normal ventilation but abnormal perfusion on lung scans, and significantly lower T cell cytotoxicity. High-dose, short-term treatment with methylprednisolone was usually effective in the reversal of the first type of rejection. In contrast, long-term maintenance prednisone therapy that was begun >30 days after transplantation was necessary to suppress the second pattern of rejection. Our study suggests that Cy A alone provides effective initial immunosuppression for use in lung allotransplantation, although corticosteroid therapy may be required after the 1st month. Preliminary data suggest that it may be possible to discontinue Cy A therapy without evidence of increased lung allograft rejection in some mongrel dogs.