Huntley, Alyson; (1997) Structure of the peripheral airways in the transplanted lung: an experimental study. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Obliterative bronchiolitis (OB) of the peripheral airways remains the most important long-term complication following lung transplantation. In the present study, the rat unilateral lung transplant model has been used. The aims were to describe the effects of preservation at 4°C, early reperfusion and transplantation on the peripheral airway structure of the lung and to investigate whether any changes persisted and might therefore be relevant to the pathogenesis of OB. Quantitative light and electron-microscopic and cell culture techniques were used. Preservation of the rat lung resulted in significant damage to the peripheral airways which increased after reperfusion. All intracellular damage had resolved by 48 hours after transplantation, although basal cell hyperplasia was present and persisted for up to 6 months after transplantation. This response was observed following both isogeneic and allogeneic transplants and was influenced by the strain and the maturity of the transplanted lung and recipient. It was also shown that peripheral airway size became greater than in age-matched controls following transplantation but that airway structure and composition were otherwise normal. This response occurred in both isogeneic and allogeneic transplants, but was greatest following allogeneic transplantation and was influenced by the maturity of the transplanted lung and recipient. The persistent basal cell hyperplasia and the increase in airway size were also observed in the recipient native non-transplanted lung but to a lesser degree, suggesting an interaction between the two lungs, possibly via humoral factors. Cultured porcine epithelial cells and fibroblasts which had been cooled to 4°C and rewarmed exhibited a greater proliferative response to fibroblast-conditioned medium than those kept at 37°C. In conclusion, single-lung transplantation led to long-term structural changes in the peripheral airways of both the transplanted and native lung. Early damage leading to basal cell hyperplasia may be important in the development of OB.

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