Postinjury thromboxane receptor blockade ameliorates acute lung injury.
BACKGROUND
Acute lung injury is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Thromboxane A2 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 A2 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 A2 receptor, even after the initiation of acute lung injury, eliminates pulmonary hypertension and improves oxygenation.
Goff
C D
CD
Department of Surgery, University of Virginia Health Sciences Center, Charlottesville 22906-0005, USA.
Corbin
R S
RS
Theiss
S D
SD
Frierson
H F
HF
Cephas
G A
GA
Tribble
C G
CG
Kron
I L
IL
Young
J S
JS
D000818:Animals; D001424:Bacterial Infections; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000150:complications / Q000517:prevention & control; D007262:Infusions, Intravenous; D008833:Microcirculation / Q000187:drug effects; D019301:Oleic Acid / Q000009:adverse effects; D010100:Oxygen / Q000097:blood; D011651:Pulmonary Artery; D011652:Pulmonary Circulation / Q000187:drug effects; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012128:Respiratory Distress Syndrome / Q000517:prevention & control*; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects
D005343:Fibrinolytic Agents; D017482:Receptors, Thromboxane; C054215:SQ 30741; D019301:Oleic Acid; D000431:Ethanol; D013928:Thromboxane A2; D010100:Oxygen