Background. Acute lung injury is associated with pulmonary hypertensio
n, intrapulmonary shunting, and increased microvascular permeability,
leading to altered oxygenation capacity. Thromboxane A(2) has been fou
nd to be a central mediator in the development of septic and oleic aci
d (OA)-induced acute lung injury. Our previous study demonstrated a be
neficial effect of preinjury thromboxane A(2) receptor blockade. The c
urrent study examines the efficacy of postinjury receptor blockade on
oxygenation capacity and pulmonary hemodynamics in an isolated lung mo
del of OA-induced acute lung injury. Methods. Four groups of rabbit he
art-lung preparations were studied for 60 minutes in an ex vivo perfus
ion-ventilation system. Saline control lungs received saline solution
during the first 20 minutes of study. Injury control lungs received an
OA-ethanol solution during the first 20 minutes. Two treatment groups
were used: T10, in which the thromboxane receptor antagonist, SQ30741
, was infused 10 minutes after the initiation of OA infusion; and T30,
in which the thromboxane receptor antagonist was infused 30 minutes a
fter OA infusion. Results. Significant differences were found in oxyge
nation (oxygen tension in T10 = 62.6 +/- 11.7 mm Hg, T30 = 68.2 +/- 21
.2 mm Hg; injury control = 40.2 +/- 9.0 mm Hg, saline control = 123.5
+/- 16.01 mm Hg; p < 0.001) and percentile change in pulmonary artery
pressure (T10 = 1.1% +/- 19.4% increase, T30 = 11.2% +/- 7.3% increase
; injury control = 47.6% +/- 20.5%, saline control = 4.2% +/- 6.81%; p
< 0.001). Conclusions. This study demonstrates that blockade of the t
hromboxane A(2) receptor, even after the initiation of acute lung inju
ry, eliminates pulmonary hypertension and improves oxygenation.