POSTINJURY THROMBOXANE RECEPTOR BLOCKADE AMELIORATES ACUTE LUNG INJURY

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.