Apoptosis has been postulated as a contributing factor in ischemia-reperfus
ion graft dysfunction following lung transplantation. The purpose of this s
tudy was to determine whether treatment with an endothrlin-A/endothrlin-B-
(ETA/ETB) receptor antagonist could reduce the level of apoptosis observed
in the lung following ischemia-reperfusion injury. Eleven dogs were subject
ed to left lung allotransplantation. Heart-lung bloch were harvested from d
onor dogs and preserved with modified Eurocollins solution and stored at 4
degreesC for 18 to 20 h. We investigated the level of apoptosis by terminal
deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), in t
he lungs of animals receiving an intravenous infusion of saline (control, n
= 5) or the ET receptor antagonist SB209670 (n = 6) (15 mug/kg/min). The i
nfusion began 30 min prior to transplantation and continued for up to 6 h t
hereafter The TUNEL staining was significantly higher in the airway epithel
ium and the parenchyma of the saline (control) group (40.67 +/- 6.16), comp
ared with native right lungs (5.00 +/- 0.56) and the treatment group (14.13
+/- 2.84). We conclude that treatment of lung allografts with the mixed ET
A/ETB-receptor antagonist SB209670 can ameliorate lung injury by reducing t
he level of apoptosis seen in the allograft following ischemia-reperfusion
injury.