EFFICACY OF ADMINISTERING AN ENDOTHELIN-RECEPTOR ANTAGONIST (SB209670) IN AMELIORATING ISCHEMIA-REPERFUSION INJURY IN LUNG ALLOGRAFTS

The purpose of this study was to determine whether treatment with an e ndothelin-1 (ET-1)-receptor antagonist could prevent ET-l-mediated isc hemia-reperfusion injury and early allograft dysfunction. Eleven dogs were subjected to left lung allotransplantation. Donor lungs were pres erved with modified Eurocollins solution and stored at 4 degrees C for 18 to 20 h. Animals received an intravenous infusion of either the ET -receptor antagonist SB209670 (n = 6) (15 mu g/kg/min) or saline (cont rol, n = 5), in a blinded fashion. The infusion started 30 min before transplantation and continued for up to 6 h after transplantation. Hem odynamic measurements, blood gas tensions, and plasma samples were obt ained with animals functioning solely on the transplanted lung. Open-l ung biopsies were obtained for wet-to-dry-weight ratios and histologic and immunohistochemical analyses. Survival at 6 h after transplantati on was 40% in the control group and 100% in the treatment group. Pulmo nary vascular resistance and lung tissue wet-to-dry-weight ratio were significantly lower in treated animals at 3 and 6 h after transplantat ion. Histology of the transplanted lungs revealed more intense airway and interstitial inflammatory infiltration and edema in the control gr oup. Arterial and venous plasma ET-1 concentrations increased after tr ansplantation; however, they were significantly higher in the treatmen t group. Immunohistochemical analysis revealed more intense ET-1 immun ostaining in the airways and parenchyma of the treatment group. We con clude that treatment of lung allografts with the mixed endothelin A/en dothelin B (ETA/ETB) receptor antagonist SB209670 can ameliorate ische mia-reperfusion injury, resulting in improved graft function and survi val after lung transplantation.