TY - JOUR
T1 - Efficacy of administering an endothelin-receptor antagonist (SB209670) in ameliorating ischemia-reperfusion injury in lung allografts
AU - Shennib, H.
AU - Lee, A. G L
AU - Kuang, J. Q.
AU - Yanagisawa, Masashi
AU - Ohlstein, E. H.
AU - Giaid, A.
PY - 1998
Y1 - 1998
N2 - The purpose of this study was to determine whether treatment with an endothelin-1 (ET-1)-receptor antagonist could prevent ET-1-mediated ischemia-reperfusion injury and early allograft dysfunction. Eleven dogs were subjected to left lung allotransplantation. Donor lungs were preserved with modified Eurocollins solution and stored at 4°C for 18 to 20 h. Animals received an intravenous infusion of either the ET-receptor antagonist SB209670 (n = 6) (15 μg/kg/min) or saline (control, n = 5), in a blinded fashion. The infusion started 30 min before transplantation and continued for up to 6 h after transplantation. Hemodynamic measurements, blood gas tensions, and plasma samples were obtained with animals functioning solely on the transplanted lung. Open-lung biopsies were obtained for wet-to-dry-weight ratios and histologic and immunohistochemical analyses. Survival at 6 h after transplantation was 40% in the control group and 100% in the treatment group. Pulmonary vascular resistance and lung tissue wet-to-dry-weight ratio were significantly lower in treated animals at 3 and 6 h after transplantation. Histology of the transplanted lungs revealed more intense airway and interstitial inflammatory infiltration and edema in the control group. Arterial and venous plasma ET-1 concentrations increased after transplantation; however, they were significantly higher in the treatment group. Immunohistochemical analysis revealed more intense ET-1 immunostaining in the airways and parenchyma of the treatment group. We conclude that treatment of lung allografts with the mixed endothelin A/endothelin B (ETA/ETB) receptor antagonist SB209670 can ameliorate ischemia-reper-fusion injury, resulting in improved graft function and survival after lung transplantation.
AB - The purpose of this study was to determine whether treatment with an endothelin-1 (ET-1)-receptor antagonist could prevent ET-1-mediated ischemia-reperfusion injury and early allograft dysfunction. Eleven dogs were subjected to left lung allotransplantation. Donor lungs were preserved with modified Eurocollins solution and stored at 4°C for 18 to 20 h. Animals received an intravenous infusion of either the ET-receptor antagonist SB209670 (n = 6) (15 μg/kg/min) or saline (control, n = 5), in a blinded fashion. The infusion started 30 min before transplantation and continued for up to 6 h after transplantation. Hemodynamic measurements, blood gas tensions, and plasma samples were obtained with animals functioning solely on the transplanted lung. Open-lung biopsies were obtained for wet-to-dry-weight ratios and histologic and immunohistochemical analyses. Survival at 6 h after transplantation was 40% in the control group and 100% in the treatment group. Pulmonary vascular resistance and lung tissue wet-to-dry-weight ratio were significantly lower in treated animals at 3 and 6 h after transplantation. Histology of the transplanted lungs revealed more intense airway and interstitial inflammatory infiltration and edema in the control group. Arterial and venous plasma ET-1 concentrations increased after transplantation; however, they were significantly higher in the treatment group. Immunohistochemical analysis revealed more intense ET-1 immunostaining in the airways and parenchyma of the treatment group. We conclude that treatment of lung allografts with the mixed endothelin A/endothelin B (ETA/ETB) receptor antagonist SB209670 can ameliorate ischemia-reper-fusion injury, resulting in improved graft function and survival after lung transplantation.
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U2 - 10.1164/ajrccm.157.6.9709131
DO - 10.1164/ajrccm.157.6.9709131
M3 - Article
C2 - 9620935
AN - SCOPUS:0031837024
SN - 1073-449X
VL - 157
SP - 1975
EP - 1981
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 6 PART I
ER -