Thromboxane receptor blockade in an animal model of ARDS

Manipulation of arachidonic acid metabolism may be important in the prevention and treatment of the adult respiratory distress syndrome. This study evaluated a thromboxane receptor blocker, BM 13.177, in a sheep endotoxin model. Sheep with chronic lung lymph fistulas were pretreated with the blocker before being given endotoxin. The blocker attenuated the early increase in pulmonary artery pressure usually seen after endotoxin (blocker + endotoxin, 31.0 +/- 14.5 mm Hg; endotoxin alone, 42.1 +/- 9.6 mm Hg). There was no effect on lymph flows during the later (permeability) phase (at 6 hours: blocker + endotoxin, 574 +/- 287% baseline; endotoxin alone, 311 +/- 102% baseline). Administration of the blocker alone increased pulmonary artery pressure, arterial pressure, and central venous pressure and decreased heart rate and cardiac index. Thromboxane receptor blockade presumably has little effect on elements of arachidonic acid metabolism other than thromboxane. Thromboxane appears to be important in the early pulmonary hypertension of the sheep endotoxin model but is relatively unimportant in the development of increased pulmonary capillary permeability.