Raised endothelin content in bronchoalveolar lavage fluid during lung allograft rejection in pigs

Various pathophysiologic mechanisms are implicated in the rejection of transplanted lungs, for example production of vasoactive substances such as endothelin. In this study the measured endothelin content of bronchoalveolar lavage (BAL) fluid was correlated to the grade of lung allograft rejection. Left lung allotransplantation was performed in seven piglets (weight 16-24 kg). Triple-drug immunosuppression (cyclosporin, azathioprine, methylprednisolone) was given, and episodes of acute rejection were induced by withdrawing the medication. The development of acute rejection was monitored with computed tomography and bronchoscopy with BAL and transbronchial biopsy. In 46 BAL samples the endothelin content was radioimmunologically assayed. Transbronchial biopsies taken simultaneously showed grade 0 rejection in 17 tissue samples, grade 1 in 21 and grade 2 in eight. The endothelin content of BAL (pg/ml) increased from 34.3 +/- 6.1 in grade 0 rejection to 54.6 +/- 6.8 in grade 1 and to 98.5 +/- 35.6 in grade 2. The increase from grade 0 was statistically significant to grade 1 (p < 0.05) and to grade 2 (p < 0.02). The increased endothelin content of BAL may have harmful effects on the lung, as endothelin is a potent vaso- and bronchoconstrictive peptide with mitogenic properties.