Postinjury Thromboxane Receptor Blockade Ameliorates Acute Lung Injury

Abstract

Background. Acute lung injury is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Thromboxane A 2 has been found to be a central mediator in the development of septic and oleic acid (OA)–induced acute lung injury. Our previous study demonstrated a beneficial effect of preinjury thromboxane A 2 receptor blockade. The current study examines the efficacy of postinjury receptor blockade on oxygenation capacity and pulmonary hemodynamics in an isolated lung model of OA-induced acute lung injury. Methods. Four groups of rabbit heart-lung preparations were studied for 60 minutes in an ex vivo perfusion-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 after OA infusion. Results. Significant differences were found in oxygenation (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 thromboxane A 2 receptor, even after the initiation of acute lung injury, eliminates pulmonary hypertension and improves oxygenation.