Original ArticlesDevelopment of obliterative bronchiolitis after allogeneic rat lung transplantation: implication of acute rejection and the time point of treatment
Section snippets
Material and methods
A total of 80 inbred, male rats underwent allogeneic (F344-to-WKY, n = 65) or syngeneic (WKY-to-WKY, n = 15) orthotopic left lung transplantation (LTX) according to standard technique.9 F344 (RT1lvl) animals served as donors and WKY (RT11) rats as recipients. The rats were obtained from Harlan-Winkelmann Laboratories (Borchen, Germany) and were specific-pathogen-free. The mean weight of the donor rats was 261.26 ± 33.08 g vs 244.00 ± 29.73 g in the recipient group. For anesthesia all animals
Results
Conventional histology showed complete normal lung tissue in the control groups without (Group 0−) or following ECS-perfusion (Group 0+). The same is true for the native right lungs in all instances and for the isografts at Day 100 in all 3 groups. There was no sign of infection or rejection.
At the 5th postoperative day only mild signs of perivascular and peribronchial infiltration without evidence of AR were found (ISHLT-score: A 0.50/B 0.20) (Figure 1). There was no damage to the vascular
Discussion
Early diagnosis and detailed knowledge about the etiology of the underlying process are the most essential preconditions to be successful in the struggle against chronic allograft dysfunction. The pathological findings of chronic lung allograft rejection are characterized by extensive fibrosis and scarring with partial respectively total occlusion of the smaller airways (obliterative bronchiolitis) or fibrointimal thickening of the arteries and veins (vascular sclerosis).10 Treatment of the CR
Conclusion
Chronic allograft dysfunction still represents the major source of late morbidity and mortality after lung transplantation. Functional impairment is based on irreversible structural changes involving the smaller bronchi and vascular structures. Several factors are thought to be of possible influence on the development of the disease. In the model studied, early acute rejection has been identified to be of significant pathogenetic causality for the generation of obliterative bronchiolitis and
Acknowledgements
The authors thank Markus Ernst, PhD for technical assistance during the study and for the statistical review.
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