Lung transplantation in the rat. A morphometric analysis of the gas exchange region

Single-lung transplantation in the rat provides a model that allows investigators to study immunologic, cellular, and morphologic changes associated with allograft rejection. We performed morphometric analysis of transplanted and nontransplanted lungs removed from recipients having received isografts, allografts, or hilus-stripping up to six months previously, and having received cyclosporine on the first postoperative day, the second postoperative day, the first five days, or not at all. When CsA was not administered, there was extensive and rapid destruction of the alveolar septa with consolidation and rejection of the transplanted lung within one week. In contrast, the allografts from rats treated with CsA were not obviously changed compared with the control lung. To evaluate whether or not these CsA-treated allografts had even subtle injury to alveolar septal cells, a morphometric analysis using transmission electron microscopy was used. There were no significant changes between control (nontransplanted or hilus-stripped) lungs and isografted or allografted lungs for most parameters measured. Exceptions included type I epithelial cell volume, which increased in rats treated with CsA on postoperative day 1 only, and the tissue component of diffusing capacity, which decreased in rats treated with CsA on postoperative day 2 only. We conclude that CsA treatment of rats given lung allografts effectively blocks the development of injury in the gas exchange region. The effect is achieved when the CsA is given during the first five days following transplantation in rats, and may be influenced by the timetable of administration and cumulative dosage.