Lung Transplantation in the Fischer 344→Wistar Kyoto Rat Strain Combination is Not Suitable to Study Bronchiolitis Obliterans

Background: To elucidate the pathogenesis of bronchiolitis obliterans (BO) a reliable animal model is needed. According to the literature, lung transplantation from Fischer 344 (17344) to Wistar Kyoto (WKY) rats is the only model that reliably results in BO without a further stimulus. Methods: We performed orthotopic left lung transplantation in F344 to WKY rats and in both isogeneic rat strain combinations. Suture and cuff techniques for anastomosis were compared. The time course of rejection and the morphology of the bronchial anastomoses were documented by repeated flat-panel volumetric computed tomography (fpVCT) in the living animal. Graft histopathology was analyzed 3 months post-transplant. Results: According to the graft outcome, as revealed by fpVCT, grafts were sub-divided into two groups: In Group 1, infiltrates due to acute rejection occurred early after transplantation and resolved thereafter. Graft histopathology showed minor changes but no BO. In Group 2, acute rejection caused total atelectasis that never resolved. After 3 months, grafts were shrunken and exhibited tissue remodeling with some similarities to BO. No correlation between graft outcome and anastomotic technique was apparent. Conclusions: Modeling lung transplantation using the F344-to-WKY combination is without clinical relevance because BO does not develop in grafts with life-sustaining function. Consecutive fpVCT is useful to monitor pathologic changes in rat pulmonary grafts.