The aim of the present study was to determine levels of endothelin-1 in bronchoalveolar lavage fluid and in plasma in patients with lung and heart- lung allografts. The aim was based on the hypothesis that levels of endothelin-1 are elevated in the bronchoalveolar lavage fluid of patients with lung allografts. Patients (n = 23) undergoing heart-lung (n = 8), single-lung (n = 10), or bilateral lung (n = 5) transplantation were included in the study. In patients with single-lung allografts, endothelin-1 levels were analyzed in bronchoalveolar lavage fluid from both the transplanted and the nontransplanted, native lung. The level of endothelin-1 was also analyzed in bronchoalveolar lavage fluid from 12 patients who did not undergo transplantation. Transbronchial biopsies and bronchoalveolar lavage were done routinely or when clinically indicated on 64 different occasions, between 2 and 104 weeks after transplantation. The level of endothelin-1 was measured in bronchoalveolar lavage fluid and plasma by radioimmunoassay. Immunoreactive endothelin-1 was detectable in bronchoalveolar lavage fluid from all patients. The concentration of endothelin-1 in bronchoalveolar lavage fluid from transplanted lungs (2.94 ± 0.30 pg/ml, n = 64) was significantly higher compared with that in bronchoalveolar lavage fluid from patients without allografts (0.86 ± 0.20 pg/ml, n = 12, p < 0.01). In patients who received single-lung transplantation because of emphysema, the level of endothelin-1 in bronchoalveolar lavage fluid from the transplanted lung was significantly greater than that from the native long (5.61 ± 1.9 versus 0.39 ± 0.05 pg/ml, p < 0.05). Concentrations of endothelin-1 in bronchoalveolar lavage fluid did not correlate with grade of rejection, infection, or time after transplant. Plasma levels of endothelin-1 were unchanged with pulmonary rejection. These results indicate that endothelin-1 is released into bronchi of transplanted human lungs. The release is not associated with rejection or infection. Because of its potent mitogenic properties, endothelin-1 may have a potential impact in the development of posttransplant complications such as bronchiolitis obliterans.
Bibliographical noteFunding Information:
Supported by grants from The Göteborg Medical Society and The Swedish National Society Association Against Heart and Lung Diseases.