Thromboxane receptor blockade improves oxygenation in an experimental model of acute lung injury.
BACKGROUND
Adult respiratory distress syndrome remains a major cause of morbidity and mortality. We investigated the role of thromboxane receptor antagonism in an experimental model of acute lung injury that mimics adult respiratory distress syndrome.


METHODS
Three groups of rabbit heart-lung preparations were studied for 30 minutes in an ex vivo blood perfusion/ventilation system. Saline control (SC) lungs received saline solution during the first 20 minutes of study. Injury control (IC) lungs received an oleic acid-ethanol solution during the first 20 minutes. Thromboxane receptor blockade (TRB) lungs received the same injury as IC lungs, but a thromboxane receptor antagonist (SQ30741) was added to the blood perfusate just prior to study. Blood gases were obtained at 10-minute intervals, and tidal volume, pulmonary artery pressure, and lung weight were continuously recorded. Oxygenation was assessed by measuring the percent change in oxygen tension over the 30-minute study period. Tissue samples were collected from all lungs for histologic evaluation.


RESULTS
Significant differences were found between SC and IC lungs as well as TRB and IC lungs when comparing pulmonary artery pressure (SC = 33.1 +/- 2.2 mm Hg, TRB = 35.4 +/- 2.1 mm Hg, IC = 60.4 +/- 11.1 mm Hg; p < 0.02) and percent change in oxygenation (SC = -20.6% +/- 10.3%, TRB = -24.2% +/- 9.5%, IC = -57.1% +/- 6.2%; p < 0.03). None of the other variables demonstrated significant differences.


CONCLUSIONS
Thromboxane receptor blockade prevents the pulmonary hypertension and the decline in oxygenation seen in an experimental model of acute lung injury that mimics adult respiratory distress syndrome.
Thies
S D
SD
Department of Surgery, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Corbin
R S
RS
Goff
C D
CD
Binns
O A
OA
Buchanan
S A
SA
Shockey
K S
KS
Frierson
H F
HF
Young
J S
JS
Tribble
C G
CG
Kron
I L
IL
D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D017482:Receptors, Thromboxane; C054215:SQ 30741; D013928:Thromboxane A2; D010100:Oxygen